, Estrogens and placental and uterus cell differentiation and proliferation 603 E2 contributes to trophoblast cell proliferation but also stimulates villous CT differentiation into STs 604 which in turn synthesize estrogens and enhance both CT proliferation and maturation (186,187)

, Estrogens modulate the fetal hypothalamic-pituitary-adrenal axis through the upregulation of placental 609

, These low fetal 610 cortisol levels stimulate ACTH release from the fetal pituitary gland which then increases DHEA 611 synthesis by the fetal adrenal glands. However, fetal adrenal glands express ER? and ER? and their 612 activity is controlled by estrogens (247), HSD11B2 (245)

. Vii and . Pe, risk factors and estrogen synthesis/signaling deficiencies 619 We reviewed available data on potential links between well-established risk factors of PE and 620 abnormal E2 synthesis and/or signaling, in order to strengthen the hypothesis that PE is associated 621 with estrogen deficiency. Maternal conditions such as obesity, diabetes and chronic hypertension, are 25 622 well known risk factors of PE (16). Similarly, the risk of PE is increased in women with renal 623 transplantation (250)

A. Obesity,

, Over two thirds of women of reproductive age are overweight or obese in the United States (251), i.e., 627 with a body mass index over 25 and 30 kg/m 2 , respectively. Central distribution of body fat (marker of 628 visceral fat) is the main risk factor for cardiovascular disease including PE (252). Adipocytes/adipose 629 tissue-resident macrophages produce estrogens by converting androgens through CYP 19

, Excessive 632 production of TNF-? and interleukin (IL)-6 by adipose tissue-resident macrophages has been 633 described in both obese pregnant and non-pregnant women (253,255). These pro-inflammatory 634 adipokines display paracrine effects (local increase of leptin synthesis) (253), promote insulin 635 resistance and participate in the systemic low-grade inflammatory state, vol.253, pp.255-258

P. E. During, Nevertheless, plasma leptin levels have 637 been found to be higher in obese women with PE than in controls (254)

, While TNF-? stimulates aromatase expression in adipose tissue stromal cells (261), leptin-mediated

, TNF-? upregulation induces an excess of CT and ST apoptosis in the placenta (262-264), thus 641 decreasing placental steroid biosynthesis

B. Diabetes,

, Chronic low-grade inflammation promotes insulin 646 resistance mainly via TNF-? and IL-6 but also via other inflammatory cytokines (268). Maternal as 647 well as fetal reactive hyperinsulinemia affect placental cells (269)

. Nestler, Uzelac et al (271) reported reduced aromatase protein concentrations but 651 no change in placental mRNA levels in women with GDM compared to those without GDM. This 652 result suggests a post-transcriptional event. Increases in insulin-like growth factor-I and II

, 274) seem to be involved as well (274), 654 though controversial results have been reported about IGFI and II plasma levels during GDM or type 2 655 diabetes, which share structural similarities with insulin, vol.273

, C. Chronic hypertension

, Based on the obesity model, we suggest that the low-grade inflammation present in CH induces 660 endothelial dysfunction and placental inflammation and could enhance placental necrosis/apoptosis 661 and insulin resistance thus contributing to E2 deficiency

D. , Kidney transplantation

, This pattern could 667 be related to numerous factors such as immune response to the grafted tissues and possibly to disease-668 related renal impairment. As described above, chronic inflammation could promote endothelial injury, 669 placental apoptosis and insulin resistance, and then facilitate the subsequent disruption of placental 670 steroidogenesis. Finally, in addition to kidney disease itself, drugs such as prednisone not only induce 671 diabetes (280) but have also been shown to enhance placental vasoconstriction, induce fetal and 672 placental growth restriction and prevent normal vascularization in rat placenta via a reduction in 673 VEGF expression (281), These patients frequently 664 gain weight early after transplantation leading to overweight or obesity (278)

, Although all these risk factors of PE can promote direct systemic endothelial injury, they also have a 676 negative impact on the placenta, including inflammation and excess of placental necrosis/apoptosis, p.27

, well as impacting aromatase production. They may thus induce an estrogen deficiency which further

, Kanasaki et al (112) successfully 682 reverted PE features with a subcutaneous administration of 2-ME2 in COMT -/-mice. Djordejvic et al 683 (284) showed that intramuscular short-term administration of E2 in women with PE reduced mean 684 arterial blood pressure. Furthermore, Genistein, a phytoestrogen with ER? selectivity as well as an 685 affinity for GPER (285,286), has also been assessed in the prevention of PE (287)

, The mechanisms of action of genistein may include GPER binding, SF1 activation and aromatase 689 modulation. The regulation of aromatase expression, and therefore its activity, is highly tissue specific

, All in all, 691 these data open up an interesting potential therapeutic field using estrogen itself or regulators of its

, Abnormal estrogen levels and dysregulation of the enzymes involved in estrogen biosynthesis have 695 been described during PE. An increasing number of studies highlight a marked decrease of estrogens 696 in maternal circulation, especially E2, the most potent ER ligand. However, published studies report 697 conflicting results possibly due to small sample sizes and mixed PE types

, Moreover, most of the studies only focus on specific targeted steroids rather than comprehensive 699 steroid profiling and also fail to assess their bioactivities. The mechanisms of E2 deficiency may 700 include changes in the regulation of expression of the main steroidogenic enzymes (aromatase, 701 HSD17B1) possibly via miRNAs and transcription factors such as USF1 and 2

, However, the major role of estrogens during physiological placental development and pregnancy 703 supports the hypothesis that low estrogen levels may play a central role in PE physiopathology

, Moreover, the close interaction between estrogens and angiogenic/antiangiogenic balance

, Further studies are required to confirm previous findings and develop clinical applications. We would 709 encourage larger studies with comprehensive steroid profiling using only analytically reliable mass 710 spectrometric procedures

, Major pending issues for clinical applications include: a) determining if estrogen deficiency is a 712 consequence of a hypoxic placenta or rather the cause or one of the initial causes of PE; b) evaluating 713 potential useful biomarkers of estrogens for PE screening and; c) assessing if natural estrogens and/or

D. A. Savitz, V. A. Danilack, S. M. Engel, B. Elston, and H. S. Lipkind, Descriptive Epidemiology of Chronic Hypertension, Gestational Hypertension, and Preeclampsia, Matern. Child Health J, vol.18, pp.829-838, 1995.

K. S. Khan, D. Wojdyla, L. Say, and A. M. Gülmezoglu, Van Look PFA. WHO analysis of causes of maternal death: a systematic review, Lancet, vol.367, pp.1066-1074, 2006.

E. V. Kuklina, C. Ayala, and W. M. Callaghan, Hypertensive disorders and severe obstetric morbidity in the United States, Obstet. Gynecol, vol.113, pp.1299-1306, 2009.

N. Berkane, Définitions et conséquences des hypertensions artérielles de la grossesse

, Ann. Fr. Anesth. Réanimation, vol.29, pp.1-6, 2010.

L. Heilmann, W. Rath, and K. Pollow, Hemostatic abnormalities in patients with severe preeclampsia, Clin. Appl. Thromb, vol.13, pp.285-291, 2007.

C. Catarino, A. Santos-silva, L. Belo, P. Rocha-pereira, S. Rocha et al., Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood, J. Pregnancy, vol.2012, pp.1-10, 2012.

C. W. Redman, G. P. Sacks, and I. L. Sargent, Preeclampsia: an excessive maternal inflammatory response to pregnancy, Am. J. Obstet. Gynecol, vol.180, pp.499-506, 1999.

Y. Zhou, M. Mcmaster, K. Woo, M. Janatpour, J. Perry et al., Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome, Am. J. Pathol, vol.160, pp.1405-1423, 2002.

A. Hertig, N. Berkane, G. Lefevre, K. Toumi, H. Marti et al., Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia, Clin. Chem, vol.50, pp.1702-1703, 2004.

R. J. Levine, S. E. Maynard, C. Qian, K. Lim, L. J. England et al.,

, Circulating angiogenic factors and the risk of preeclampsia, N. Engl. J. Med, vol.350, pp.672-683, 2004.

S. E. Maynard, J. Min, J. Merchan, K. Lim, J. Li et al., Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia, J. Clin. Invest, vol.111, pp.649-658, 2003.

R. N. Taylor, J. Grimwood, R. S. Taylor, M. T. Mcmaster, S. J. Fisher et al., Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies, Am. J. Obstet. Gynecol, vol.188, pp.177-182, 2003.

V. Tsatsaris, F. Goffin, C. Munaut, J. Brichant, M. Pignon et al., Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences, J. Clin. Endocrinol. Metab, vol.88, pp.5555-5563, 2003.

V. Tsatsaris, F. Goffin, and J. M. Foidart, Circulating angiogenic factors and preeclampsia, N. Engl. J. Med, vol.350, 2003.

C. Redman and I. L. Sargent, Placental stress and pre-eclampsia: a revised view, Placenta, vol.30, 2009.

C. W. Redman and I. L. Sargent, Latest advances in understanding preeclampsia, Science, vol.308, pp.1592-1594, 2005.

C. A. Labarrere, Acute atherosis. A histopathological hallmark of immune aggression?, Placenta, vol.9, pp.95-108, 1988.

D. T. Lowe, Nitric oxide dysfunction in the pathophysiology of preeclampsia, Nitric Oxide Biol. Chem, vol.4, pp.441-458, 2000.

G. Chen, S. H. Wang, H. Z. Zheng, J. J. Walker, and J. H. Mckillop, Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia, Clin. Exp. Immunol, vol.104, pp.154-159, 1996.

S. Y. Lau, S. Guild, C. J. Barrett, Q. Chen, L. Mccowan et al., Tumor necrosis factor-alpha, interleukin-6, and interleukin-10 levels are altered in preeclampsia: a systematic review and meta-analysis, Am. J. Reprod. Immunol, vol.70, pp.412-427, 2013.

G. S. Vince, P. M. Starkey, R. Austgulen, D. Kwiatkowski, and C. W. Redman, Interleukin-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with pre-eclampsia, Br. J. Obstet. Gynaecol, vol.102, pp.20-25, 1995.

J. M. Roberts, R. N. Taylor, T. J. Musci, G. M. Rodgers, C. A. Hubel et al.,

, Gynäkol, vol.25, pp.2-6, 1992.

G. M. Rodgers, R. N. Taylor, and J. M. Roberts, Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells, Am. J. Obstet. Gynecol, vol.159, pp.908-914, 1988.

C. R. Rosenfeld and R. Rivera, Circulatory responses to systemic infusions of estrone and estradiol-17alpha in nonpregnant, oophorectomized ewes, Am. J. Obstet. Gynecol, vol.132, pp.442-448, 1978.

T. Caulin-glaser, G. García-cardeña, P. Sarrel, W. C. Sessa, and J. R. Bender, 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization, Circ. Res, vol.81, pp.885-892, 1997.

K. Hisamoto, M. Ohmichi, H. Kurachi, J. Hayakawa, Y. Kanda et al., Estrogen induces the Aktdependent activation of endothelial nitric-oxide synthase in vascular endothelial cells, J. Biol. Chem, vol.276, pp.3459-3467, 2001.

T. Simoncini, A. R. Genazzani, and J. K. Liao, Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene, Circulation, vol.105, pp.1368-1373, 2002.

K. Cullinan-bove and R. D. Koos, Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with 32 estrogen-induced increases in uterine capillary permeability and growth, Endocrinology, vol.133, pp.829-837, 1993.

M. Hervé, .. J. Meduri, G. Petit, F. G. Domet, T. S. Lazennec et al., Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus, J. Endocrinol, vol.188, pp.91-99, 2006.

J. L. Shifren, J. F. Tseng, C. J. Zaloudek, I. P. Ryan, Y. G. Meng et al., Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis, J. Clin. Endocrinol. Metab, vol.81, pp.3112-3118, 1996.

M. L. Johnson, A. T. Grazul-bilska, D. A. Redmer, and L. P. Reynolds, Effects of estradiol-17beta on expression of mRNA for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX) ewes, Endocrine, vol.30, pp.333-342, 2006.

G. Shanker, M. Sorci-thomas, and M. R. Adams, Estrogen modulates the expression of tumor necrosis factor alpha mRNA in phorbol ester-stimulated human monocytic THP-1 cells

, Lymphokine Cytokine Res, vol.13, pp.377-382, 1994.

A. D. Notation and G. E. Tagatz, Unconjugated estriol and 15alpha-hydroxyestriol in complicated pregnancies, Am. J. Obstet. Gynecol, vol.128, pp.747-756, 1977.

S. A. Rahman, V. Hingorani, and K. R. Laumas, Biosynthesis of oestrogens and their interconversion in human placentae from normal and toxaemic pregnancies, Clin. Endocrinol, vol.4, pp.333-341, 1975.

U. Rosing and K. Carlström, Serum levels of unconjugated and total oestrogens and dehydroepiandrosterone, progesterone and urinary oestriol excretion in pre-eclampsia

, Gynecol. Obstet. Invest, vol.18, pp.199-205, 1984.

S. Zamudio, K. K. Leslie, M. White, D. D. Hagerman, and L. G. Moore, Low serum estradiol and high serum progesterone concentrations characterize hypertensive pregnancies at high altitude, J. Soc. Gynecol. Investig, vol.1, pp.197-205, 1994.

A. Hertig, P. Liere, N. Chabbert-buffet, J. Fort, A. Pianos et al.,

, Am. J. Obstet. Gynecol, vol.203, pp.477-478, 2010.

S. O. Jobe, C. T. Tyler, and R. R. Magness, Aberrant synthesis, metabolism, and plasma accumulation of circulating estrogens and estrogen metabolites in preeclampsia implications for vascular dysfunction, Hypertension, vol.61, pp.480-487, 2013.

D. J. Handelsman and L. Wartofsky, Requirement for mass spectrometry sex steroid assays in the, Journal of Clinical Endocrinology and Metabolism. J. Clin. Endocrinol. Metab, vol.98, pp.3971-3973, 2013.

A. E. Palmer, W. T. London, D. L. Sly, and J. M. Rice, Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas), Lab. Anim. Sci, vol.29, pp.102-106, 1979.

L. Krugner-higby, M. Luck, D. Hartley, H. M. Crispen, G. R. Lubach et al., High-risk pregnancy in rhesus monkeys ( Macaca mulatta ): a case of ectopic, abdominal pregnancy with birth of a live, term infant, and a case of gestational diabetes complicated by pre-eclampsia, J. Med. Primatol, vol.38, pp.252-256, 2009.

A. Hennessy, A. G. Gillin, D. M. Painter, P. J. Kirwan, J. F. Thompson et al., Evidence for Preeclampsia in a Baboon Pregnancy with Twins, Hypertens. Pregnancy, vol.16, pp.223-228, 1997.

E. Staun-ram and E. Shalev, Human trophoblast function during the implantation process, Reprod. Biol. Endocrinol, vol.3, p.56, 2005.

O. D. Genbacev, A. Prakobphol, R. A. Foulk, A. R. Krtolica, D. Ilic et al., Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface, Science, vol.299, pp.405-408, 2003.

J. Challier and S. Uzan,

, Médecine Sci, vol.19, pp.1111-1120, 2003.

P. Merviel, J. C. Challier, L. Carbillon, J. M. Foidart, and S. Uzan, The role of integrins in human embryo implantation, Fetal Diagn. Ther, vol.16, pp.364-371, 2001.

Y. Zhou, S. J. Fisher, M. Janatpour, O. Genbacev, E. Dejana et al., Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?, J. Clin. Invest, vol.99, pp.2139-2151, 1997.

A. E. Wallace, R. Fraser, and J. E. Cartwright, Extravillous trophoblast and decidual natural killer cells: a remodelling partnership, Hum. Reprod. Update, vol.18, pp.458-471, 2012.

G. Whitley and J. E. Cartwright, Trophoblast-mediated spiral artery remodelling: a role for apoptosis, J. Anat, vol.215, pp.21-26, 2009.

L. X. Liu, H. Lu, Y. Luo, T. Date, A. J. Belanger et al., Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1, Biochem. Biophys. Res. Commun, vol.291, pp.908-914, 2002.

T. Wheeler, C. L. Elcock, and F. W. Anthony, Angiogenesis and the placental environment, Placenta, vol.16, pp.289-296, 1995.

R. Pijnenborg, L. Vercruysse, and M. Hanssens, The Uterine Spiral Arteries In Human Pregnancy: Facts and Controversies, Placenta, vol.27, pp.939-958, 2006.

D. Goldman-wohl and S. Yagel, Regulation of trophoblast invasion: from normal implantation to pre-eclampsia, Mol. Cell. Endocrinol, vol.187, pp.233-238, 2002.

M. Knight, C. W. Redman, E. A. Linton, and I. L. Sargent, Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies, Br. J. Obstet. Gynaecol, vol.105, pp.632-640, 1998.

C. Tse, G. Lefevre, N. Berkane, A. Flahault, K. Toumi et al., Increased serum maternal levels of the HER2 oncoprotein p105 ectodomain in preeclampsia, Clin. Chem. Lab. Med, vol.42, pp.142-146, 2004.

T. Nagamatsu, T. Fujii, M. Kusumi, L. Zou, T. Yamashita et al., Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 the pathophysiology of preeclampsia, Endocrinology, vol.145, pp.4838-4845, 2004.

H. Li, B. Gu, Y. Zhang, D. F. Lewis, and Y. Wang, Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta, Placenta, vol.26, pp.210-217, 2005.

S. Hofmann, H. Grasberger, P. Jung, M. Bidlingmaier, J. Vlotides et al., The tumour necrosis factor-alpha induced vascular permeability is associated with a reduction of VE-cadherin expression, Eur. J. Med. Res, vol.7, pp.171-176, 2002.

A. M. Carter, A. C. Enders, and R. Pijnenborg, The role of invasive trophoblast in implantation and placentation of primates, Philos. Trans. R. Soc. Lond. B. Biol. Sci, vol.370, 2015.

P. Devroey, M. Camus, G. Palermo, J. Smitz, L. Van-waesberghe et al., Placental production of estradiol and progesterone after oocyte donation in patients with primary ovarian failure, Am. J. Obstet. Gynecol, vol.162, pp.66-70, 1990.

V. D. Castracane and J. W. Goldzieher, Timing of the luteal-placental shift in the baboon (Papio cynocephalus), Endocrinology, vol.118, pp.506-512, 1986.

M. Levitz and B. K. Young, Estrogens in pregnancy, Vitam. Horm, vol.35, pp.109-147, 1977.

M. Abbassi-ghanavati, L. G. Greer, and F. G. Cunningham, Pregnancy and laboratory studies: a reference table for clinicians, Obstet. Gynecol, vol.114, pp.1326-1331, 2009.

R. E. Oakey, The progressive increase in estrogen production in human pregnancy: an appraisal of the factors responsible, Vitam. Horm, vol.28, pp.1-36, 1970.

Z. Tang, S. Tadesse, E. Norwitz, G. Mor, V. M. Abrahams et al., Isolation of hofbauer cells from human term placentas with high yield and purity, Am. J. Reprod. Immunol, vol.66, pp.336-348, 2011.

M. Schmidt, M. Kreutz, G. Löffler, J. Schölmerich, and R. H. Straub, Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages, J. Endocrinol, vol.164, pp.161-169, 2000.

J. C. Escobar, S. S. Patel, V. E. Beshay, T. Suzuki, and B. R. Carr, The human placenta expresses CYP17 and generates androgens de novo, J. Clin. Endocrinol. Metab, vol.96, pp.1385-1392, 2011.

R. Pion, R. Jaffe, G. Eriksson, N. Wiqvist, and E. Diczfalusy, Studies on the metabolism of C-21 steroids in the human foetoplacental unit. I. Formation of a beta-unsaturated 3-ketones in midterm placentas perfused in situ with pregnenolone and 17-alphahydroxypregnenolone, Acta Endocrinol, vol.48, pp.234-248, 1965.

P. K. Siiteri and P. C. Macdonald, Placental estrogen biosynthesis during human pregnancy, J. Clin. Endocrinol. Metab, vol.26, pp.751-761, 1966.

C. N. Falany, J. Wheeler, T. S. Oh, and J. L. Falany, Steroid sulfation by expressed human cytosolic sulfotransferases, J. Steroid Biochem. Mol. Biol, vol.48, pp.369-375, 1994.

P. K. Siiteri, The continuing saga of dehydroepiandrosterone (DHEA), J. Clin. Endocrinol. Metab, vol.90, pp.3795-3796, 2005.

M. Peter, H. G. Dörr, and W. G. Sippell, Changes in the concentrations of dehydroepiandrosterone sulfate and estriol in maternal plasma during pregnancy: a longitudinal study in healthy women throughout gestation and at term, Horm. Res, vol.42, pp.278-281, 1994.

E. C. Salido, P. H. Yen, L. Barajas, and L. J. Shapiro, Steroid sulfatase expression in human placenta: immunocytochemistry and in situ hybridization study, J. Clin. Endocrinol

, Metab, vol.70, pp.1564-1567, 1990.

M. Mizuno, J. Lobotsky, C. W. Lloyd, T. Kobayashi, and Y. Murasawa, Plasma androstenedione and testerone during pregnancy and in the newborn, J. Clin. Endocrinol. Metab, vol.28, pp.1133-1142, 1968.

M. A. Rivarola, M. G. Forest, and C. J. Migeon, Testosterone, androstenedione and dehydroepiandrosterone in plasma during pregnancy and at delivery: concentration and protein binding, J. Clin. Endocrinol. Metab, vol.28, pp.34-40, 1968.

H. J. Ruder, L. Loriaux, and M. B. Lipsett, Estrone sulfate: production rate and metabolism in man, J. Clin. Invest, vol.51, pp.1020-1033, 1972.

J. W. Mueller, L. C. Gilligan, J. Idkowiak, W. Arlt, and P. A. Foster, The Regulation of Steroid Action by Sulfation and Desulfation, Endocr. Rev, vol.36, pp.526-563, 2015.

C. C. Calzada-mendoza, E. C. Sánchez, R. R. Campos, A. M. Becerril, E. B. Madrigal et al., Differential aromatase (CYP19) expression in human arteries from normal and neoplasic uterus: an immunohistochemical and in situ hybridization study, Front. Biosci. J. Virtual Libr, vol.11, pp.389-393, 2006.

M. Bonenfant, P. R. Provost, R. Drolet, and Y. Tremblay, Localization of type 1 17beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi, J. Endocrinol, vol.165, pp.217-222, 2000.

E. D. Albrecht and G. J. Pepe, Placental steroid hormone biosynthesis in primate pregnancy, Endocr. Rev, vol.11, pp.124-150, 1990.

N. Yoshida and Y. Osawa, Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization, Biochemistry (Mosc.), vol.30, pp.3003-3010, 1991.

S. M. Mackenzie, S. S. Huda, N. Sattar, R. Fraser, J. Connell et al., Depot-specific steroidogenic gene transcription in human adipose tissue, Clin. Endocrinol, vol.69, pp.848-854, 2008.

G. J. Pepe and E. D. Albrecht, Actions of placental and fetal adrenal steroid hormones in primate pregnancy, Endocr. Rev, vol.16, pp.608-648, 1995.

B. Husen, J. Adamski, A. Brüns, D. Deluca, K. Fuhrmann et al., Characterization of 17beta-hydroxysteroid dehydrogenase type 7 in reproductive tissues of the marmoset monkey, Biol. Reprod, vol.68, pp.2092-2099, 2003.

L. Milewich, P. C. Macdonald, and B. R. Carr, Estrogen 16 alpha-hydroxylase activity in human fetal tissues, J. Clin. Endocrinol. Metab, vol.63, pp.404-406, 1986.

E. A. Zbella, J. Ilekis, A. Scommegna, and R. Benveniste, Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion, J. Clin. Endocrinol. Metab, vol.63, pp.751-757, 1986.

R. Cantineau, P. Kremers, J. De-graeve, J. E. Gielen, and R. Lambotte, 15-and 16-hydroxylations of androgens and estrogens in the human fetal liver: a critical step in estetrol biosynthesis, J. Steroid Biochem, vol.22, pp.195-201, 1985.

E. Gurpide, J. Schwers, M. T. Welch, R. L. Vande-wiele, and S. Lieberman, Fetal and maternal metabolism of estradiol during pregnancy, J. Clin. Endocrinol. Metab, vol.26, pp.1355-1365, 1966.

C. F. Holinka, E. Diczfalusy, C. Bennink, and H. , Estetrol: a unique steroid in human pregnancy, J. Steroid Biochem. Mol. Biol, vol.110, pp.138-143, 2008.

J. Schwers, G. Eriksson, and E. Diczfalusy, 15alpha-hydroxylation: a new pathway of estrogen metabolism in the human fetus and newborn, Biochim. Biophys. Acta, vol.100, pp.313-316, 1965.

L. Benassi, L. Alfieri, D. Debiasi, and R. Trentadue, Unconjugated estetrol in normal pregnancy, Clin. Exp. Obstet. Gynecol, vol.9, pp.243-245, 1982.

A. Abot, C. Fontaine, M. Buscato, R. Solinhac, G. Flouriot et al., The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor ? modulation, uncoupling nuclear and membrane activation, EMBO Mol. Med, vol.6, pp.1328-1346, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01118038

N. Pluchino, A. N. Santoro, E. Casarosa, A. Giannini, A. Genazzani et al., Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats, J. Steroid Biochem. Mol. Biol, vol.143, pp.285-290, 2014.

C. Bennink, H. Verhoeven, C. Zimmerman, Y. Visser, M. Foidart et al., Clinical effects of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women, Maturitas, vol.91, pp.93-100, 2016.

R. K. Dubey, D. G. Gillespie, L. C. Zacharia, F. Barchiesi, B. Imthurn et al., CYP450-and COMT-derived estradiol metabolites inhibit activity of human coronary artery SMCs, Hypertension, vol.41, pp.807-813, 2003.

R. K. Dubey, S. P. Tofovic, and E. K. Jackson, Cardiovascular pharmacology of estradiol metabolites, J. Pharmacol. Exp. Ther, vol.308, pp.403-409, 2004.

S. O. Jobe, J. Ramadoss, J. M. Koch, Y. Jiang, J. Zheng et al., Estradiol-17beta and its cytochrome P450-and catechol-O-methyltransferase-derived metabolites stimulate proliferation in uterine artery endothelial cells: role of estrogen receptor-alpha versus estrogen receptor-beta, Hypertension, vol.55, pp.1005-1011, 2010.

S. L. Stice, S. P. Ford, J. P. Rosazza, and D. E. Van-orden, Interaction of 4-hydroxylated estradiol and potential-sensitive Ca2+ channels in altering uterine blood flow during the estrous cycle and early pregnancy in gilts, Biol. Reprod, vol.36, pp.369-375, 1987.

A. J. Lee, M. X. Cai, P. E. Thomas, A. H. Conney, and B. T. Zhu, Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms, Endocrinology, vol.144, pp.3382-3398, 2003.

M. L. Casey and P. C. Macdonald, Characterization of catechol-O-methyltransferase activity in human uterine decidua vera tissue, Am. J. Obstet. Gynecol, vol.145, pp.453-457, 1983.

N. Gamage, A. Barnett, N. Hempel, R. G. Duggleby, K. F. Windmill et al., Human sulfotransferases and their role in chemical metabolism, Toxicol. Sci, vol.90, pp.5-22, 2006.

Y. Miki, T. Nakata, T. Suzuki, A. D. Darnel, T. Moriya et al., Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues, J. Clin. Endocrinol. Metab, vol.87, pp.5760-5768, 2002.

M. H. Tong, H. Jiang, P. Liu, J. A. Lawson, L. F. Brass et al., Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferase-deficient mice, Nat. Med, vol.11, pp.153-159, 2005.

A. Aitio, UDPglucuronosyltransferase of the human placenta, Biochem. Pharmacol, vol.23, pp.2203-2205, 1974.

P. Paakki, H. Stockmann, M. Kantola, P. Wagner, U. Lauper et al., Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro, Environ. Health Perspect, vol.108, pp.141-145, 2000.

J. D. Yager and N. E. Davidson, Estrogen carcinogenesis in breast cancer, N. Engl. J. Med, vol.354, pp.270-282, 2006.

G. Yin, X. Zhu, C. Guo, Y. Yang, T. Han et al., Differential expression of estradiol and estrogen receptor ? in severe preeclamptic pregnancies compared with normal pregnancies, Mol. Med. Rep, vol.7, pp.981-985, 2013.

S. Bussen and D. Bussen, Influence of the vascular endothelial growth factor on the development of severe pre-eclampsia or HELLP syndrome, Arch. Gynecol. Obstet, vol.284, pp.551-557, 2011.

S. P. Salas, G. Marshall, B. L. Gutiérrez, and P. Rosso, Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction, Hypertension, vol.47, pp.203-208, 2006.

S. Aç?kgöz, U. O. Bayar, M. Can, B. Güven, G. Mungan et al., Levels of oxidized LDL, estrogens, and progesterone in placenta tissues and serum paraoxonase activity in preeclampsia, Mediators Inflamm, p.862982, 2013.

Y. Zhang, T. Wang, Y. Shen, X. Wang, P. N. Baker et al., 2-Methoxyestradiol deficiency is strongly related to hypertension in early onset severe pre-eclampsia, Pregnancy Hypertens, vol.4, pp.215-219, 2014.

K. Kanasaki, K. Palmsten, H. Sugimoto, S. Ahmad, Y. Hamano et al., Deficiency in catechol-Omethyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia, Nature, vol.453, issue.7198, pp.1117-1121, 2008.

A. Pérez-sepúlveda, M. J. Torres, F. J. Valenzuela, R. Larraín, H. Figueroa-diesel et al., Low 2-methoxyestradiol levels at the first trimester of pregnancy are associated with the development of pre-eclampsia

, Diagn, vol.32, pp.1053-1058, 2012.

M. Pertegal, F. J. Fenoy, M. Hernández, J. Mendiola, J. L. Delgado et al., Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia, Fertil. Steril, vol.105, pp.134-143, 2016.

Z. Shen, Y. Wu, X. Chen, X. Chang, Q. Zhou et al., Decreased maternal serum 2-methoxyestradiol levels are associated with the development of preeclampsia, Cell. Physiol. Biochem, vol.34, pp.2189-2199, 2014.

H. Seol, G. Cho, M. Oh, and H. Kim, 2-methoxyoestradiol levels and placental catechol-O-methyltransferase expression in patients with late-onset preeclampsia, Arch. Gynecol. Obstet, vol.287, pp.881-886, 2013.

F. Sharifzadeh, M. Kashanian, and F. Fatemi, A comparison of serum androgens in preeclamptic and normotensive pregnant women during the third trimester of pregnancy

, Gynecol. Endocrinol, vol.28, pp.834-836, 2012.

J. D. Martin, M. E. Hähnel, and R. Hähnel, Plasma androstenedione in normotensive and hypertensive pregnancy, Steroids, vol.48, pp.315-329, 1986.

N. Harada, T. Utsumi, and Y. Takagi, Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis, Proc. Natl. Acad. Sci. U. S. A, vol.90, pp.11312-11316, 1993.

L. Kragie, Aromatase in primate pregnancy: a review, Endocr. Res, vol.28, pp.121-128, 2002.

K. Toda, E. R. Simpson, C. R. Mendelson, Y. Shizuta, and M. W. Kilgore, Expression of the gene encoding aromatase cytochrome P450 (CYP19) in fetal tissues, Mol. Endocrinol, vol.8, pp.210-217, 1994.

S. Nakajin, M. Shinoda, and P. F. Hall, Purification to homogeneity of aromatase from human placenta, Biochem. Biophys. Res. Commun, vol.134, pp.704-710, 1986.

A. Kamat, J. L. Alcorn, C. Kunczt, and C. R. Mendelson, Characterization of the regulatory regions of the human aromatase (P450arom) gene involved in placenta-specific expression, Mol. Endocrinol, vol.12, pp.1764-1777, 1998.

P. Kumar, A. Kamat, and C. R. Mendelson, Estrogen receptor alpha (ERalpha) mediates stimulatory effects of estrogen on aromatase (CYP19) gene expression in human placenta, Mol. Endocrinol, vol.23, pp.784-793, 2009.

N. Fournet-dulguerov, N. J. Maclusky, C. Z. Leranth, R. Todd, C. R. Mendelson et al., Immunohistochemical localization of aromatase cytochrome P-450 and estradiol dehydrogenase in the syncytiotrophoblast of the human placenta, J. Clin. Endocrinol. Metab, vol.65, issue.4, pp.757-764, 1987.

P. Kumar, Y. Luo, C. Tudela, J. M. Alexander, and C. R. Mendelson, The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation, Mol. Cell. Biol, vol.33, pp.1782-1796, 2013.

B. Jiang and C. R. Mendelson, USF1 and USF2 mediate inhibition of human trophoblast differentiation and CYP19 gene expression by Mash-2 and hypoxia, Mol. Cell. Biol, vol.23, pp.6117-6128, 2003.

S. M. Charles, C. G. Julian, E. Vargas, and L. G. Moore, Higher Estrogen Levels During Pregnancy in Andean Than European Residents of High Altitude Suggest Differences in Aromatase Activity, J. Clin. Endocrinol. Metab, vol.99, pp.2908-2916, 2014.

M. E. Hähnel, J. D. Martin, C. A. Michael, and R. Hähnel, Metabolism of androstenedione by placental microsomes in pregnancy hypertension, Clin. Chim. Acta, vol.181, pp.103-108, 1989.

M. Shimodaira, T. Nakayama, I. Sato, N. Sato, N. Izawa et al., Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy, Endocrine, vol.42, pp.700-707, 2012.

J. Moon, M. H. Moon, K. T. Kim, D. H. Jeong, Y. N. Kim et al., Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures, J. Steroid Biochem. Mol. Biol, vol.139, pp.182-191, 2014.

A. Perez-sepulveda, L. J. Monteiro, A. Dobierzewska, P. P. España-perrot, P. Venegas-araneda et al., Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia, PloS One, vol.10, p.139682, 2015.

S. C. Moore, C. E. Matthews, O. Shu, X. , Y. K. Gail et al., Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women, J. Natl. Cancer Inst, vol.108, 2016.

C. X. Ma, A. A. Adjei, O. E. Salavaggione, J. Coronel, L. Pelleymounter et al., Human aromatase: gene resequencing and functional genomics, Cancer Res, vol.65, pp.11071-11082, 2005.

S. E. Bulun, Aromatase and estrogen receptor ? deficiency, Fertil. Steril, vol.101, pp.323-329, 2014.

A. Hauri-hohl, M. Meyer-böni, M. Lang-muritano, M. Hauri-hohl, E. J. Schoenle et al., Aromatase deficiency owing to a functional variant in the placenta promoter and a novel missense mutation in the CYP19A1 gene, Clin. Endocrinol, vol.75, pp.39-43, 2011.

P. E. Mullis, N. Yoshimura, B. Kuhlmann, K. Lippuner, P. Jaeger et al., Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood, J. Clin. Endocrinol. Metab, vol.82, pp.1739-1745, 1997.

B. Ludwikowski, S. Heger, N. Datz, A. Richter-unruh, and R. González, Aromatase deficiency: rare cause of virilization, Eur. J. Pediatr. Surg, vol.23, pp.418-422, 2013.

M. Maliqueo, B. Echiburú, and N. Crisosto, Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes, Front. Physiol, vol.7, p.152, 2016.

D. P. Sieveking, P. Lim, R. Chow, L. L. Dunn, S. Bao et al., A sex-specific role for androgens in angiogenesis, J. Exp. Med, vol.207, pp.345-352, 2010.

S. Henríquez, P. Kohen, X. Xu, T. D. Veenstra, A. Muñoz et al., Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity, Fertil. Steril, vol.106, pp.230-237, 2016.

T. Rabe, R. Hösch, and B. Runnebaum, Sulfatase deficiency in the human placenta: clinical findings, Biol. Res. Pregnancy Perinatol, vol.4, pp.95-102, 1983.

O. Ishibashi, A. Ohkuchi, M. M. Ali, R. Kurashina, S. Luo et al., Hydroxysteroid (17-?) dehydrogenase 1 is 45 dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia, Hypertension, vol.59, pp.265-273, 2012.

A. Ohkuchi, O. Ishibashi, C. Hirashima, K. Takahashi, S. Matsubara et al., Plasma level of hydroxysteroid (17-?) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fmslike tyrosine kinase 1/placental growth factor ratio, Hypertens. Res. Off. J. Jpn. Soc. Hypertens, vol.35, pp.1152-1158, 2012.

Y. Li, V. Isomaa, A. Pulkka, R. Herva, H. Peltoketo et al., Expression of 3beta-hydroxysteroid dehydrogenase type 1, P450 aromatase, and 17beta-hydroxysteroid dehydrogenase types 1, 2, 5 and 7 mRNAs in human early and mid-gestation placentas, Placenta, vol.26, pp.387-392, 2005.

T. Saloniemi, H. Jokela, L. Strauss, P. Pakarinen, and M. Poutanen, The diversity of sex steroid action: novel functions of hydroxysteroid (17?) dehydrogenases as revealed by genetically modified mouse models, J. Endocrinol, vol.212, pp.27-40, 2012.

H. C. Guldberg and C. A. Marsden, Catechol-O-methyl transferase: pharmacological aspects and physiological role, Pharmacol. Rev, vol.27, pp.135-206, 1975.

J. Tenhunen, M. Salminen, A. Jalanko, S. Ukkonen, and I. Ulmanen, Structure of the rat catechol-O-methyltransferase gene: separate promoters are used to produce mRNAs for soluble and membrane-bound forms of the enzyme, DNA Cell Biol, vol.12, pp.253-263, 1993.

S. M. Salih, S. A. Salama, A. A. Fadl, M. Nagamani, A. et al., Expression and cyclic variations of catechol-O-methyl transferase in human endometrial stroma, Fertil. Steril, vol.90, pp.789-797, 2008.

S. A. Salama, M. Jamaluddin, R. Kumar, M. H. Hassan, A. et al., Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: distinct effect of progesterone receptor isoforms, J. Steroid Biochem. Mol. Biol, vol.107, pp.253-261, 2007.

S. Liang, X. Liu, P. Fan, R. Liu, J. Zhang et al., Association between Val158Met functional polymorphism in the COMT gene and risk of preeclampsia in a Chinese population, Arch. Med. Res, vol.43, pp.154-158, 2012.

J. H. Lim, S. Y. Kim, D. J. Kim, S. Y. Park, H. W. Han et al., Genetic polymorphism of catechol-O-methyltransferase and cytochrome P450c17 ? in preeclampsia, Pharmacogenet. Genomics, vol.20, pp.605-610, 2010.

L. D. Hill, T. P. York, J. P. Kusanovic, R. Gomez, L. J. Eaves et al., Epistasis between COMT and MTHFR in maternal-fetal dyads increases risk for preeclampsia, PloS One, vol.6, p.16681, 2011.

L. T. Roten, M. H. Fenstad, S. Forsmo, M. P. Johnson, E. K. Moses et al., A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2), Mol. Hum. Reprod, vol.17, pp.439-446, 2011.

E. R. Barnea, N. J. Maclusky, A. H. Decherney, and F. Naftolin, Catechol-o-methyl transferase activity in the human term placenta, Am. J. Perinatol, vol.5, pp.121-127, 1988.

K. Palmer, B. Saglam, C. Whitehead, O. Stock, M. Lappas et al., Severe early-onset preeclampsia is not associated with a change in placental catechol O-methyltransferase (COMT) expression, Am. J. Pathol, vol.178, pp.2484-2488, 2011.

E. Grouzmann, C. Cavadas, D. Grand, M. Moratel, A. Brunner et al., Blood sampling methodology is crucial for precise measurement of plasma catecholamines concentrations in mice, Arch. Eur. J. Physiol, vol.447, pp.254-258, 2003.

M. Böttner, P. Thelen, and H. Jarry, Estrogen receptor beta: tissue distribution and the still largely enigmatic physiological function, J. Steroid Biochem. Mol. Biol, vol.139, pp.245-251, 2014.

S. Chakraborty, H. Willett, and P. K. Biswas, Insight into estrogen receptor beta-beta and alpha-beta homo-and heterodimerization: A combined molecular dynamics and sequence analysis study, Biophys. Chem, vol.170, pp.42-50, 2012.

C. J. Gruber, W. Tschugguel, C. Schneeberger, and J. C. Huber, Production and actions of estrogens, N. Engl. J. Med, vol.346, pp.340-352, 2002.

G. G. Kuiper, B. Carlsson, K. Grandien, E. Enmark, J. Häggblad et al., Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta, Endocrinology, vol.138, pp.863-870, 1997.

L. A. Helguero, M. H. Faulds, J. Gustafsson, and L. Haldosén, Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11, Oncogene, vol.24, pp.6605-6616, 2005.

J. A. Gustafsson and M. Warner, Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer, J. Steroid Biochem. Mol. Biol, vol.74, pp.245-248, 2000.

J. A. Gustafsson, Estrogen receptor beta--a new dimension in estrogen mechanism of action, J. Endocrinol, vol.163, pp.379-383, 1999.

M. Beato and J. Klug, Steroid hormone receptors: an update, Hum. Reprod. Update, vol.6, pp.225-236, 2000.

S. W. Curtis, T. Washburn, C. Sewall, R. Diaugustine, J. Lindzey et al., Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor, Proc. Natl. Acad. Sci. U. S. A, vol.93, pp.12626-12630, 1996.

R. Kumar, M. N. Zakharov, S. H. Khan, R. Miki, H. Jang et al., The dynamic structure of the estrogen receptor, J. Amino Acids, p.812540, 2011.

C. J. Gruber, D. M. Gruber, I. Gruber, F. Wieser, and J. C. Huber, Anatomy of the estrogen response element, Trends Endocrinol. Metab. TEM, vol.15, pp.73-78, 2004.

L. Klein-hitpass, G. U. Ryffel, E. Heitlinger, and A. C. Cato, A 13 bp palindrome is a functional estrogen responsive element and interacts specifically with estrogen receptor, Nucleic Acids Res, vol.16, pp.647-663, 1988.

J. R. Schultz, L. N. Petz, and A. M. Nardulli, Cell-and ligand-specific regulation of promoters containing activator protein-1 and Sp1 sites by estrogen receptors alpha and beta, J. Biol. Chem, vol.280, pp.347-354, 2005.

N. Heldring, G. D. Isaacs, A. G. Diehl, M. Sun, E. Cheung et al., Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway, Mol. Endocrinol, vol.25, pp.564-574, 2011.

E. R. Barnea, N. J. Maclusky, and F. Naftolin, Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity, Steroids, vol.41, pp.643-656, 1983.

M. Gupta, A. Mcdougal, and S. Safe, Estrogenic and antiestrogenic activities of 16alpha-and 2-hydroxy metabolites of 17beta-estradiol in MCF-7 and T47D human breast cancer cells, J. Steroid Biochem. Mol. Biol, vol.67, pp.413-419, 1998.

J. Schneider, M. M. Huh, H. L. Bradlow, and J. Fishman, Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells, J. Biol. Chem, vol.259, pp.4840-4845, 1984.

C. P. Martucci and J. Fishman, Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion, Endocrinology, vol.105, pp.1288-1292, 1979.

T. Fotsis, Y. Zhang, M. S. Pepper, H. Adlercreutz, R. Montesano et al., The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth, Nature, vol.368, pp.237-239, 1994.

S. Dimmeler, I. Fleming, B. Fisslthaler, C. Hermann, R. Busse et al., Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation, Nature, vol.399, pp.601-605, 1999.

M. P. Haynes, D. Sinha, K. S. Russell, M. Collinge, D. Fulton et al., Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells, Circ. Res, vol.87, pp.677-682, 2000.

A. Alvarez, C. Hermenegildo, A. C. Issekutz, J. V. Esplugues, and M. Sanz, Estrogens inhibit angiotensin II-induced leukocyte-endothelial cell interactions in vivo via rapid endothelial nitric oxide synthase and cyclooxygenase activation, Circ. Res, vol.91, pp.1142-1150, 2002.

S. O. Jobe, J. Ramadoss, A. J. Wargin, and R. R. Magness, Estradiol-17? and its cytochrome P450-and catechol-O-methyltransferase-derived metabolites selectively stimulate production of prostacyclin in uterine artery endothelial cells: role of estrogen receptor-? versus estrogen receptor-?, Hypertens, vol.61, pp.509-518, 2013.

T. Padayachi, R. J. Pegoraro, L. Rom, and S. M. Joubert, Enzyme immunoassay of oestrogen and progesterone receptors in uterine and intrauterine tissue during human pregnancy and labour, J. Steroid Biochem. Mol. Biol, vol.37, pp.509-511, 1990.

M. Perrot-applanat, M. Deng, H. Fernandez, C. Lelaidier, G. Meduri et al., Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels, J. Clin. Endocrinol. Metab, vol.78, pp.216-224, 1994.

W. G. Rossmanith, S. Wolfahrt, A. Ecker, and E. Eberhardt, The demonstration of progesterone, but not of estrogen, receptors in the developing human placenta

, Metab. Res. Horm, vol.29, pp.604-610, 1997.

G. Taddei, I. Noei, E. Periti, P. Borri, F. Torricelli et al., Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy, Gynecol. Obstet. Invest, vol.42, pp.77-79, 1996.

W. X. Wu, X. H. Ma, G. C. Smith, and P. W. Nathanielsz, Differential distribution of ERalpha and ERbeta mRNA in intrauterine tissues of the pregnant rhesus monkey, Am. J. Physiol. Cell Physiol, vol.278, pp.190-198, 2000.

A. Bukovsky, M. Cekanova, M. R. Caudle, J. Wimalasena, J. S. Foster et al., Expression and localization of estrogen receptor-alpha protein in normal and abnormal 50 term placentae and stimulation of trophoblast differentiation by estradiol, Reprod. Biol. Endocrinol, vol.1, p.13, 2003.

A. Bukovsky, M. R. Caudle, M. Cekanova, R. I. Fernando, J. Wimalasena et al., Placental expression of estrogen receptor beta and its hormone binding variant--comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells, Reprod. Biol

, Endocrinol, vol.1, p.36, 2003.

M. A. Younes, N. F. Besch, and P. K. Besch, Estradiol and progesterone binding in human term placental cytosol, Am. J. Obstet. Gynecol, vol.141, pp.170-174, 1981.

C. Dasgupta, M. Chen, H. Zhang, S. Yang, and L. Zhang, Chronic hypoxia during gestation causes epigenetic repression of the estrogen receptor-? gene in ovine uterine arteries via heightened promoter methylation, Hypertension, vol.60, pp.697-704, 2012.

C. Tessier, S. Deb, A. Prigent-tessier, S. Ferguson-gottschall, G. B. Gibori et al., Estrogen receptors alpha and beta in rat decidua cells: cell-specific expression and differential regulation by steroid hormones and prolactin, Endocrinology, vol.141, pp.3842-3851, 2000.

T. Welsh, M. Johnson, L. Yi, H. Tan, R. Rahman et al., Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ER? activates ERK1/2 signaling in term myometrium, J. Endocrinol, vol.212, pp.227-238, 2012.

M. B. Pastore, S. O. Jobe, J. Ramadoss, and R. R. Magness, Estrogen receptor-? and estrogen receptor-? in the uterine vascular endothelium during pregnancy: functional implications for regulating uterine blood flow, Semin. Reprod. Med, vol.30, pp.46-61, 2012.

M. J. Byers, A. Zangl, T. M. Phernetton, G. Lopez, D. Chen et al., Endothelial vasodilator production by ovine uterine and systemic arteries: ovarian steroid and pregnancy control of ERalpha and ERbeta levels, J. Physiol, vol.565, pp.85-99, 2005.

A. Molvarec, A. Vér, A. Fekete, K. Rosta, L. Derzbach et al., Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe preeclampsia, Hypertens. Res, vol.30, pp.205-211, 2007.

J. Zhang, H. Bai, X. Liu, P. Fan, R. Liu et al., Genotype distribution of estrogen receptor alpha polymorphisms in pregnant women from healthy and preeclampsia populations and its relation to blood pressure levels

, Chem. Lab. Med, vol.47, pp.391-397, 2009.

M. J. Cudmore, P. W. Hewett, S. Ahmad, K. Wang, M. Cai et al., The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis, Nat. Commun, vol.3, p.972, 2012.

M. D. Mueller, J. L. Vigne, A. Minchenko, D. I. Lebovic, D. C. Leitman et al., Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta, Proc. Natl. Acad. Sci. U. S. A, vol.97, pp.10972-10977, 2000.

P. Bausero, M. Ben-mahdi, J. Mazucatelli, C. Bloy, and M. Perrot-applanat, Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia, Am. J. Physiol. Heart Circ. Physiol, vol.279, pp.2033-2042, 2000.

D. E. Morales, K. A. Mcgowan, D. S. Grant, S. Maheshwari, D. Bhartiya et al., Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model, Circulation, vol.91, pp.755-763, 1995.

D. W. Losordo and J. M. Isner, Estrogen and angiogenesis: A review, Arterioscler. Thromb. Vasc. Biol, vol.21, pp.6-12, 2001.

M. B. Rauschemberger, M. J. Sandoval, and V. L. Massheimer, Cellular and molecular actions displayed by estrone on vascular endothelium, Mol. Cell. Endocrinol, vol.339, pp.136-143, 2011.

D. Holmes and Z. I. , Placental growth factor induces FosB and c-Fos gene expression via Flt-1 receptors, FEBS Lett, vol.557, pp.93-98, 2004.

D. Menendez, A. Inga, J. Snipe, O. Krysiak, G. Schönfelder et al., A singlenucleotide polymorphism in a half-binding site creates p53 and estrogen receptor control of vascular endothelial growth factor receptor 1, Mol. Cell. Biol, vol.27, pp.2590-2600, 2007.

C. E. Gargett, M. Zaitseva, K. Bucak, S. Chu, P. J. Fuller et al., 17Beta-estradiol upregulates vascular endothelial growth factor receptor-2 expression in human myometrial microvascular endothelial cells: role of estrogen receptor-alpha and -beta, J. Clin. Endocrinol. Metab, vol.87, pp.4341-4349, 2002.

H. H. Hou, S. L. Cheng, H. T. Liu, F. Z. Yang, H. C. Wang et al., Elastase induced lung epithelial cell apoptosis and emphysema through placenta growth factor, Cell Death Dis, vol.4, p.793, 2013.

Z. Zhang, K. G. Neiva, M. W. Lingen, L. M. Ellis, and J. E. Nör, VEGF-dependent tumor angiogenesis requires inverse and reciprocal regulation of VEGFR1 and VEGFR2, Cell Death Differ, vol.17, pp.499-512, 2010.

S. Jaffer, O. Shynlova, and S. Lye, Mammalian target of rapamycin is activated in association with myometrial proliferation during pregnancy, Endocrinology, vol.150, pp.4672-4680, 2009.

O. Shynlova, P. Tsui, A. Dorogin, B. L. Langille, and S. J. Lye, Insulin-like growth factors and their binding proteins define specific phases of myometrial differentiation during pregnancy in the rat, Biol. Reprod, vol.76, pp.571-578, 2007.

O. Shynlova, P. Tsui, S. Jaffer, and S. J. Lye, Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour, Eur. J. Obstet

. Gynecol, Reprod. Biol, vol.144, issue.1, pp.2-10, 2009.

N. J. Mabjeesh, D. Escuin, T. M. Lavallee, V. S. Pribluda, G. M. Swartz et al., , p.53

J. A. Forsythe, B. H. Jiang, N. V. Iyer, F. Agani, S. W. Leung et al., Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1

, Mol. Cell. Biol, vol.16, pp.4604-4613, 1996.

A. Perez-sepulveda, P. P. España-perrot, E. R. Norwitz, and S. E. Illanes, Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia, Reprod. Sci, vol.20, pp.1020-1029, 2013.

I. Thaler, D. Manor, J. Itskovitz, S. Rottem, N. Levit et al., Changes in uterine blood flow during human pregnancy, Am. J. Obstet. Gynecol, vol.162, pp.121-125, 1990.

W. C. Mabie, T. G. Disessa, L. G. Crocker, B. M. Sibai, and K. L. Arheart, A longitudinal study of cardiac output in normal human pregnancy, Am. J. Obstet. Gynecol, vol.170, pp.849-856, 1994.

S. M. Mone, S. P. Sanders, and S. D. Colan, Control mechanisms for physiological hypertrophy of pregnancy, Circulation, vol.94, pp.667-672, 1996.

D. C. Merrill, M. Karoly, K. Chen, C. M. Ferrario, and K. B. Brosnihan, Angiotensin-(1-7) in normal and preeclamptic pregnancy, Endocrine, vol.18, pp.239-245, 2002.

M. C. Chappell, A. C. Marshall, E. M. Alzayadneh, H. A. Shaltout, and D. I. Diz, Update on the Angiotensin converting enzyme 2-Angiotensin (1-7)-MAS receptor axis: fetal programing, sex differences, and intracellular pathways, Front. Endocrinol, vol.4, p.201, 2014.

H. L. Rupnow, T. M. Phernetton, C. E. Shaw, M. L. Modrick, I. M. Bird et al., Endothelial vasodilator production by uterine and systemic arteries. VII. Estrogen and progesterone effects on eNOS, Am. J. Physiol. Heart Circ. Physiol, vol.280, pp.1699-1705, 2001.

H. L. Rupnow, T. M. Phernetton, M. L. Modrick, M. C. Wiltbank, I. M. Bird et al., Endothelial vasodilator production by uterine and systemic arteries. VIII. Estrogen and progesterone effects on cPLA2, COX-1, and PGIS protein expression, Biol. Reprod, vol.66, pp.468-474, 2002.

R. Resnik, A. P. Killam, F. C. Battaglia, E. L. Makowski, and G. Meschia, The stimulation of uterine blood flow by various estrogens, Endocrinology, vol.94, pp.1192-1196, 1974.

M. Barbagallo, L. J. Dominguez, G. Licata, J. Shan, L. Bing et al., Vascular Effects of Progesterone : Role of Cellular Calcium Regulation, Hypertension, vol.37, pp.142-147, 2001.

S. L. Miller, G. Jenkin, and D. W. Walker, Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe, Am. J. Obstet. Gynecol, vol.180, pp.1138-1145, 1999.

R. R. Magness, J. A. Sullivan, Y. Li, T. M. Phernetton, and I. M. Bird, Endothelial vasodilator production by uterine and systemic arteries. VI. Ovarian and pregnancy effects on eNOS and NO(x), Am. J. Physiol. Heart Circ. Physiol, vol.280, pp.1692-1698, 2001.

S. H. Nelson, O. S. Steinsland, Y. Wang, C. Yallampalli, Y. L. Dong et al., Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy, Circ. Res, vol.87, pp.406-411, 2000.

J. M. Storment, M. Meyer, and G. Osol, Estrogen augments the vasodilatory effects of vascular endothelial growth factor in the uterine circulation of the rat, Am. J. Obstet. Gynecol, vol.183, pp.449-453, 2000.

H. Kimura and H. Esumi, Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis, Acta Biochim. Pol, vol.50, pp.49-59, 2003.

S. Montgomery, L. Shaw, N. Pantelides, M. Taggart, and C. Austin, Acute effects of oestrogen receptor subtype-specific agonists on vascular contractility, Br. J. Pharmacol, vol.139, pp.1249-1253, 2003.

J. B. Salom, M. C. Burguete, F. J. Pérez-asensio, G. Torregrosa, and E. Alborch, Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition, J. Cereb. Blood Flow Metab, vol.21, pp.422-429, 2001.

J. M. Orshal and R. A. Khalil, Gender, sex hormones, and vascular tone, Am. J. Physiol. Regul. Integr. Comp. Physiol, vol.286, pp.233-249, 2004.

G. B. Stefano, V. Prevot, J. C. Beauvillain, P. Cadet, C. Fimiani et al., Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia, Circulation, vol.101, pp.1594-1597, 2000.

D. J. Darkow, L. Lu, and R. E. White, Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cGMP, Am. J. Physiol, vol.272, pp.2765-2773, 1997.

W. H. Clewell, B. A. Carson, and G. Meschia, Comparison of uterotrophic and vascular effects of estradiol-17beta and estriol in the mature organism, Am. J. Obstet. Gynecol, vol.129, pp.384-388, 1977.

M. G. Levine, M. Miodovnik, and K. E. Clark, Uterine vascular effects of estetrol in nonpregnant ewes, Am. J. Obstet. Gynecol, vol.148, pp.735-738, 1984.

R. Hilgers, S. Oparil, W. Wouters, C. Bennink, and H. , Vasorelaxing effects of estetrol in rat arteries, J. Endocrinol, vol.215, pp.97-106, 2012.

D. Berg, F. Thaler, and E. Kuss, Concentrations of 2-hydroxyoestrogens in human sera measured by a heterologous immunoassay with an 125I-labelled ligand, Acta Endocrinol, vol.100, pp.154-160, 1982.

D. Berg, R. Sonsalla, and E. Kuss, Concentrations of 2-methoxyoestrogens in human serum measured by a heterologous immunoassay with an 125I-labelled ligand, Acta Endocrinol, vol.103, pp.282-288, 1983.

S. B. Lee, A. P. Wong, K. Kanasaki, Y. Xu, V. K. Shenoy et al., Preeclampsia: 2-methoxyestradiol induces cytotrophoblast invasion and vascular development specifically under hypoxic conditions, Am. J. Pathol, vol.176, pp.710-720, 2010.

R. K. Dubey and E. K. Jackson, Potential vascular actions of 2-methoxyestradiol, Trends Endocrinol. Metab, vol.20, pp.374-379, 2009.

S. M. Lobmaier, F. Figueras, I. Mercade, F. Crovetto, A. Peguero et al., Levels of maternal serum angiogenic factors in third-56 trimester normal pregnancies: reference ranges, influence of maternal and pregnancy factors and fetoplacental Doppler indices, Fetal Diagn. Ther, vol.36, pp.38-43, 2014.

S. Baggia, E. D. Albrecht, and G. J. Pepe, Regulation of 11 beta-hydroxysteroid dehydrogenase activity in the baboon placenta by estrogen, Endocrinology, vol.126, pp.2742-2748, 1990.

Z. S. Krozowski and J. W. Funder, Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity, Proc. Natl. Acad. Sci. U. S. A, vol.80, pp.6056-6060, 1983.

E. Schoof, M. Girstl, W. Frobenius, M. Kirschbaum, H. G. Dörr et al., Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia

, J. Clin. Endocrinol. Metab, vol.86, pp.1313-1317, 2001.

P. He, Z. Chen, Q. Sun, Y. Li, H. Gu et al., Reduced expression of 11?-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPAR? but increased PPAR? expression, Endocrinology, vol.155, pp.299-309, 2014.

B. Dahlstrøm, P. Romundstad, P. Øian, L. J. Vatten, and A. Eskild, Placenta weight in preeclampsia, Acta Obstet. Gynecol. Scand, vol.87, pp.608-611, 2008.

G. J. Pepe and E. D. Albrecht, Comparison of cortisol-cortisone interconversion in vitro by the human and baboon placenta, Steroids, vol.44, pp.229-240, 1984.

K. M. Doody, B. R. Carr, W. E. Rainey, W. Byrd, B. A. Murry et al., 3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland, Endocrinology, vol.126, pp.2487-2492, 1990.

J. Kaludjerovic and W. E. Ward, The Interplay between Estrogen and Fetal Adrenal Cortex, J. Nutr. Metab, p.837901, 2012.

E. D. Albrecht, J. S. Babischkin, W. A. Davies, M. G. Leavitt, and G. J. Pepe, Identification and developmental expression of the estrogen receptor alpha and beta in the baboon fetal adrenal gland, Endocrinology, vol.140, pp.5953-5961, 1999.

E. D. Albrecht, G. W. Aberdeen, and G. J. Pepe, Estrogen elicits cortical zone-specific effects on development of the primate fetal adrenal gland, Endocrinology, vol.146, pp.1737-1744, 2005.

K. Bramham, C. Nelson-piercy, H. Gao, M. Pierce, N. Bush et al., Pregnancy in renal transplant recipients: a UK national cohort study, Clin. J. Am. Soc. Nephrol, vol.8, pp.290-298, 2013.

K. M. Flegal, M. D. Carroll, C. L. Ogden, and L. R. Curtin, Prevalence and trends in obesity among US adults, JAMA, vol.303, pp.235-241, 1999.

J. M. Roberts, L. M. Bodnar, T. E. Patrick, and R. W. Powers, The role of obesity in preeclampsia. Pregnancy Hypertens, Int. J. Womens Cardiovasc. Health, vol.1, issue.1, pp.6-16, 2011.

J. N. Fain, Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells, Vitam. Horm, vol.74, pp.443-477, 2006.

A. Turgut, A. Ozler, N. Y. Goruk, S. Y. Tunç, M. E. Sak et al., Serum levels of the adipokines, free fatty acids, and oxidative stress markers in obese and nonobese preeclamptic patients, Clin. Exp. Obstet. Gynecol, vol.42, pp.473-479, 2015.

A. H. Berg and P. E. Scherer, Adipose tissue, inflammation, and cardiovascular disease, Circ. Res, vol.96, pp.939-949, 2005.

J. K. Sethi and G. S. Hotamisligil, The role of TNF alpha in adipocyte metabolism, Semin. Cell Dev. Biol, vol.10, pp.19-29, 1999.

P. A. Kern, S. Ranganathan, C. Li, L. Wood, and G. Ranganathan, Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance

, Am. J. Physiol. Endocrinol. Metab, vol.280, pp.745-751, 2001.

S. E. Shoelson, J. Lee, and A. B. Goldfine, Inflammation and insulin resistance, J. Clin. Invest, vol.116, pp.1793-1801, 2006.

K. Miehle, H. Stepan, and M. Fasshauer, Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia, Clin. Endocrinol, vol.76, pp.2-11, 2012.

A. C. Palei, F. T. Spradley, and J. P. Granger, Chronic hyperleptinemia results in the development of hypertension in pregnant rats, Am. J. Physiol. Regul. Integr. Comp. Physiol, vol.308, pp.855-861, 2015.

Y. Zhao, J. E. Nichols, R. Valdez, C. R. Mendelson, and E. R. Simpson, Tumor necrosis factoralpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4, Mol. Endocrinol, vol.10, pp.1350-1357, 1996.

L. Higgins, T. A. Mills, S. L. Greenwood, E. J. Cowley, C. P. Sibley et al., Maternal obesity and its effect on placental cell turnover, J. Matern.-Fetal Neonatal Med, vol.26, pp.783-788, 2013.

S. Haider and M. Knöfler, Human Tumour Necrosis Factor: Physiological and Pathological Roles in Placenta and Endometrium, Placenta, vol.30, pp.111-123, 2009.

M. I. Garcia-lloret, B. Winkler-lowen, and L. J. Guilbert, Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce local apoptosis via release of TNF-alpha. A model for hematogenous initiation of placental inflammations, J. Leukoc. Biol, vol.68, pp.903-908, 2000.

R. Coya, P. Martul, J. Algorta, M. A. Aniel-quiroga, M. A. Busturia et al., Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells, Gynecol. Endocrinol, vol.22, pp.620-626, 2006.

, Diagnosis and classification of diabetes mellitus, Diabetes Care, vol.27, issue.1, pp.5-10, 2004.

K. Kaul, M. Apostolopoulou, and M. Roden, Insulin resistance in type 1 diabetes mellitus, Metabolism, vol.64, pp.1629-1639, 2015.

K. Makki, P. Froguel, and I. Wolowczuk, Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines. ISRN Inflamm, vol.2013, pp.1-12, 2013.

G. Desoye and S. Hauguel-de-mouzon, The human placenta in gestational diabetes mellitus. The insulin and cytokine network, Diabetes Care, vol.30, issue.2, pp.120-126, 2007.

D. J. Mcrobie, K. R. Korzekwa, D. D. Glover, and T. S. Tracy, The effects of diabetes on placental aromatase activity, J. Steroid Biochem. Mol. Biol, vol.63, pp.147-153, 1997.

P. S. Uzelac, X. Li, J. Lin, L. D. Neese, L. Lin et al., Dysregulation of Leptin and Testosterone Production and Their Receptor Expression in the Human Placenta with Gestational Diabetes Mellitus, Placenta, vol.31, pp.581-588, 2010.

A. Morisset, M. Dubé, R. Drolet, M. Pelletier, F. Labrie et al., Androgens in the maternal and fetal circulation: association with insulin resistance, J. Matern.-Fetal Neonatal Med, vol.26, pp.513-519, 2013.

J. E. Nestler, Modulation of aromatase and P450 cholesterol side-chain cleavage enzyme activities of human placental cytotrophoblasts by insulin and insulin-like growth factor I, Endocrinology, vol.121, pp.1845-1852, 1987.

J. E. Nestler, Regulation of the aromatase activity of human placental cytotrophoblasts by insulin, insulin-like growth factor-I, and -II, J. Steroid Biochem. Mol. Biol, vol.44, pp.449-457, 1993.

H. J. Schneider, N. Friedrich, J. Klotsche, S. Schipf, M. Nauck et al., Prediction of incident diabetes mellitus by baseline IGF1 levels, Eur. J. Endocrinol, vol.164, pp.223-229, 2011.

E. W. Seely and J. Ecker, Chronic Hypertension in Pregnancy, Circulation, vol.129, p.1254, 2014.

I. Barbosa, W. Silva, G. Cerqueira, N. F. Novo, F. A. Almeida et al.,

, Maternal and fetal outcome in women with hypertensive disorders of pregnancy: the 349 impact of prenatal care, Ther Adv Cardiovasc Dis, vol.9, pp.140-146, 2015.

K. S. Khan, D. Wojdyla, L. Say, and A. M. Gülmezoglu, Van Look PFA. WHO analysis of 351 causes of maternal death: a systematic review, Lancet, vol.367, pp.1066-74, 2006.

D. A. Savitz, V. A. Danilack, S. M. Engel, B. Elston, and H. S. Lipkind, Descriptive Epidemiology 353 of Chronic Hypertension, Gestational Hypertension, and Preeclampsia, p.354

. State, Maternal and Child Health Journal, vol.18, pp.829-867, 1995.

J. M. Schutte, N. Schuitemaker, J. Van-roosmalen, E. Steegers, and .. P. , Dutch Maternal, p.356

M. Committee, Substandard care in maternal mortality due to hypertensive 357 disease in pregnancy in the Netherlands, BJOG, vol.115, pp.732-738, 2008.

A. B. Andersgaard, A. Herbst, M. Johansen, A. Ivarsson, I. Ingemarsson et al., Eclampsia in Scandinavia: incidence, substandard care, and potentially 360 preventable cases, Acta Obstet Gynecol Scand, vol.85, pp.929-965, 2006.

L. Ghulmiyyah and B. Sibai, Maternal mortality from preeclampsia/eclampsia, Semin 362 Perinatol, vol.36, pp.56-65, 2012.

Y. Giguère, M. Charland, E. Bujold, N. Bernard, S. Grenier et al., Combining 364 biochemical and ultrasonographic markers in predicting preeclampsia: a systematic 365 review, Clin Chem, vol.56, pp.361-75, 2010.

F. Milne, C. Redman, J. Walker, P. Baker, J. Bradley et al., The pre-eclampsia 367 community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia 368 in the community, BMJ, vol.330, pp.576-80, 2005.

C. Visintin, M. A. Mugglestone, M. Q. Almerie, L. M. Nherera, D. James et al.,

, Management of hypertensive disorders during pregnancy: summary of NICE 371 guidance, BMJ, vol.341, p.2207, 2010.

C. Redman, Hypertension in pregnancy: the NICE guidelines, Heart, vol.373, pp.1967-1976, 2011.

T. Gillon, A. Pels, P. Von-dadelszen, K. Macdonell, and L. A. Magee, Hypertensive 375 disorders of pregnancy: a systematic review of international clinical practice 376 guidelines, PLoS ONE, vol.9, p.113715, 2014.

, American College of Obstetricians and Gynecologists, Task Force on Hypertension in

. Pregnancy, Report of the American College of 379

G. Obstetricians, Task Force on Hypertension in Pregnancy, Gynecol, vol.380, pp.1122-1153, 2013.

L. A. Magee, A. Pels, M. Helewa, R. E. Von-dadelszen, and P. , Canadian Hypertensive 382 Disorders of Pregnancy Working Group. Diagnosis, evaluation, and management of 383 the hypertensive disorders of pregnancy: executive summary, J Obstet Gynaecol Can, vol.384, pp.416-457, 2014.

. Group, Clinical risk factors for pre-eclampsia determined in early pregnancy: 387 systematic review and meta-analysis of large cohort studies, 15. WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and 389, vol.353, 2016.

. Eclampsia and . Geneva, World Health Organization, 2011.

L. Verghese, S. Alam, S. Beski, R. Thuraisingham, I. Barnes et al., Antenatal 391 screening for pre-eclampsia: evaluation of the NICE and pre-eclampsia community 392 guidelines, J Obstet Gynaecol, vol.32, pp.128-159, 2012.

K. S. Khan, D. Wojdyla, L. Say, A. M. Gülmezoglu, and P. F. , Van Look, WHO analysis of causes of maternal death: a systematic review, Lancet, vol.367, issue.9516, pp.1066-1074, 2006.

E. V. Kuklina, C. Ayala, and W. M. Callaghan, Hypertensive disorders and severe obstetric morbidity in the United States, Obstet. Gynecol, vol.113, issue.6, pp.1299-1306, 2009.

S. A. Karumanchi, Angiogenic factors in preeclampsia: from diagnosis to therapy, Hypertension, vol.67, issue.6, pp.1072-1079, 2016.

H. Stepan, I. Herraiz, D. Schlembach, S. Verlohren, S. Brennecke et al., Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice, Ultrasound Obstet. Gynecol, vol.45, issue.3, pp.241-246, 2015.

S. Verlohren, I. Herraiz, O. Lapaire, D. Schlembach, H. Zeisler et al., New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/ placental growth factor ratio as a diagnostic test for preeclampsia, Hypertension, vol.63, issue.2, pp.346-352, 2014.

H. Zeisler, M. O. Sator, and E. A. Joura, Serum levels of progesterone in patients with preeclampsia, Wien Klin. Wochenschr, vol.112, issue.8, pp.362-364, 2000.

S. Rana, S. A. Karumanchi, and M. D. Lindheimer, Angiogenic factors in diagnosis, management, and research in preeclampsia, Hypertension, vol.63, issue.2, pp.198-202, 2014.

A. Hertig, P. Liere, N. Chabbert-buffet, J. Fort, A. Pianos et al., Steroid profiling in preeclamptic women: evidence for aromatase deficiency, Am. J. Obstet. Gynecol, vol.203, issue.5, pp.1-9, 2010.

N. Berkane, P. Liere, J. Oudinet, A. Hertig, G. Lefèvre et al., From pregnancy to preeclampsia: a key role for estrogens, Endocr. Rev, vol.38, issue.2, pp.123-144, 2017.

R. Pion, R. Jaffe, G. Eriksson, N. Wiqvist, and E. Diczfalusy, Studies on the metabolism of C-21 steroids in the human feto-placental unit.I. Formation of a beta-unsaturated 3-ketones in midterm placentas perfused in situ with pregnenolone and 17-alphahydroxypregnenolone, Acta Endocrinol, vol.48, pp.234-248, 1965.

P. K. Siiteri and P. C. Macdonald, Placental estrogen biosynthesis during human pregnancy, J. Clin. Endocrinol. Metab, vol.26, issue.7, pp.751-761, 1966.

M. Levitz and B. K. Young, Estrogens in pregnancy, Vitam. Horm, vol.35, pp.109-147, 1977.

M. Abbassi-ghanavati, L. G. Greer, and F. G. Cunningham, Pregnancy and laboratory studies: a reference table for clinicians, Obstet. Gynecol, vol.114, issue.6, pp.1326-1331, 2009.

D. Tulchinsky and D. M. Okada, Hormones in human pregnancy. IV. Plasma progesterone, vol.121, pp.293-299, 1975.

J. Shan, L. M. Resnick, Q. Y. Liu, X. C. Wu, M. Barbagallo et al., Vascular effects of 17 beta-estradiol in male Sprague-Dawley rats, Am. J. Physiol, vol.266, issue.3, pp.967-973, 1994.

M. D. Mueller, J. L. Vigne, E. A. Pritts, V. Chao, E. Dreher et al., Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells, Fertil. Steril, vol.79, issue.2, pp.386-392, 2003.

M. Maliqueo, B. Echiburú, and N. Crisosto, Sex steroids modulate uterine-placental vasculature: implications for Obstetrics and neonatal outcomes, Front. Physiol, vol.7, p.152, 2016.

A. Bukovsky, M. R. Caudle, M. Cekanova, R. I. Fernando, J. Wimalasena et al., Placental expression of estrogen receptor beta and its hormone binding variant-comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells, Reprod. Biol. Endocrinol, vol.1, p.36, 2003.

A. Bukovsky, M. Cekanova, M. R. Caudle, J. Wimalasena, J. S. Foster et al., Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol, Reprod. Biol. Endocrinol, vol.1, p.13, 2003.

D. W. Losordo and J. M. Isner, Estrogen and angiogenesis: a review, Arterioscler. Thromb. Vasc. Biol, vol.21, issue.1, pp.6-12, 2001.

N. Berkane, Placenta xxx, 2018.

A. Das, S. R. Mantena, A. Kannan, D. B. Evans, M. K. Bagchi et al., De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis, Proc. Natl. Acad. Sci. U. S. A, vol.106, issue.30, pp.12542-12547, 2009.

A. Perez-sepulveda, L. J. Monteiro, A. Dobierzewska, P. P. España-perrot, P. Venegas-araneda et al., Irarrazabal, H. Figueroa-Diesel, M. Varas-Godoy, S.E. Illanes, Placental aromatase is deficient in placental ischemia and preeclampsia, vol.10, p.139682, 2015.

D. J. Roberts and M. D. Post, The placenta in pre-eclampsia and intrauterine growth restriction, J. Clin. Pathol, vol.61, issue.12, pp.1254-1260, 2008.

P. Von-dadelszen, L. A. Magee, and J. M. Roberts, Subclassification of preeclampsia, Hypertens, Pregnancy, vol.22, issue.2, pp.143-148, 2003.

N. Berkane, Définitions et conséquences des hypertensions artérielles de la grossesse, vol.29, pp.1-6, 2010.

N. Yoshida and Y. Osawa, Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization, Biochemistry, vol.30, issue.12, pp.3003-3010, 1991.

H. Peltoketo, V. Luu-the, J. Simard, and J. Adamski, 17beta-hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the 17HSD/KSR enzymes, J. Mol. Endocrinol, vol.23, issue.1, pp.1-11, 1999.

K. Sathishkumar, M. Balakrishnan, V. Chinnathambi, M. Chauhan, G. D. Hankins et al., Fetal sex-related dysregulation in testosterone production and their receptor expression in the human placenta with preeclampsia, J. Perinatol, vol.32, issue.5, pp.328-335, 2012.

S. Bussen and D. Bussen, Influence of the vascular endothelial growth factor on the development of severe pre-eclampsia or HELLP syndrome, Arch. Gynecol. Obstet, vol.284, issue.3, pp.551-557, 2011.

O. Ishibashi, A. Ohkuchi, M. M. Ali, R. Kurashina, S. Luo et al., Hydroxysteroid (17-?) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia, Hypertension, vol.59, issue.2, pp.265-273, 2012.

A. Ohkuchi, O. Ishibashi, C. Hirashima, K. Takahashi, S. Matsubara et al., Plasma level of hydroxysteroid (17-?) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio, Hypertens. Res, vol.35, issue.12, pp.1152-1158, 2012.

X. Shao, Y. Liu, M. Liu, Y. Wang, L. Yan et al.,

. Wang, Testosterone represses estrogen signaling by upregulating miR-22: a mechanism for imbalanced steroid hormone production in preeclampsia, Hypertension, vol.69, issue.4, pp.721-730, 2017.

B. Jiang and C. R. Mendelson, USF1 and USF2 mediate inhibition of human trophoblast differentiation and CYP19 gene expression by Mash-2 and hypoxia, Mol. Cell Biol, vol.23, issue.17, pp.6117-6128, 2003.

M. Shimodaira, T. Nakayama, I. Sato, N. Sato, N. Izawa et al., Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy, Endocrine, vol.42, issue.3, pp.700-707, 2012.

R. Hampl and L. Starka, Minireview: 16alpha-hydroxylated metabolites of dehydroepiandrosterone and their biological significance, Endocr. Regul, vol.34, issue.3, pp.161-163, 2000.

K. Kanasaki, K. Palmsten, H. Sugimoto, S. Ahmad, Y. Hamano et al., Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia, Nature, vol.453, issue.7198, pp.1117-1121, 2008.

S. W. Walsh, Progesterone and estradiol production by normal and preeclamptic placentas, Obstet. Gynecol, vol.71, issue.2, pp.222-226, 1988.

S. Luisi, F. Petraglia, C. Benedetto, R. E. Nappi, F. Bernardi et al., Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients, J. Clin. Endocrinol. Metab, vol.85, issue.7, pp.2429-2433, 2000.

M. Quinkler, S. Johanssen, C. Bumke-vogt, W. Oelkers, V. Bähr et al., Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney, Mol. Cell. Endocrinol, vol.171, issue.1-2, pp.21-24, 2001.

R. P. Piekorz, S. Gingras, A. Hoffmeyer, J. N. Ihle, and Y. Weinstein, Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20?-hydroxysteroid dehydrogenase, Mol. Endocrinol, vol.19, issue.2, pp.431-440, 2005.

M. Quinkler, B. Meyer, C. Bumke-vogt, C. Grossmann, U. Gruber et al., Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor, Eur. J. Endocrinol, vol.146, issue.6, pp.789-799, 2002.

D. J. Handelsman and L. Wartofsky, Requirement for mass spectrometry sex steroid assays in the, Journal of Clinical Endocrinology and Metabolism, vol.98, issue.10, pp.3971-3973, 2013.

Y. Osawa, B. Tochigi, M. Tochigi, S. Ohnishi, Y. Watanabe et al., Aromatase inhibitors in cigarette smoke, tobacco leaves and other plants, J. Enzym. Inhib, vol.4, issue.2, pp.187-200, 1990.

T. Ishida, F. Seo, K. Hirato, T. Fukuda, T. Yanaihara et al., Changes in placental enzymatic activities in relation to estrogen production during pregnancy, Nippon. Sanka Fujinka Gakkai Zasshi, vol.37, issue.4, pp.547-554, 1985.

G. J. Burton, H. Yung, T. Cindrova-davies, and D. S. Charnock-jones, Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia, Placenta, vol.30, pp.43-48, 2009.

, Les références en italique précédées de * sont : des revues, mises au point, opinion, ou recommandations, les autres références sont des articles originaux

*. Abbassi-ghanavati, M. Greer, L. G. Cunningham, and F. G. , Pregnancy and laboratory studies: a reference table for clinicians, Obstet Gynecol, vol.114, pp.1326-1331, 2009.

F. Acconcia, A. Bocedi, P. Ascenzi, and M. Marino, Does palmitoylation target estrogen receptors to plasma membrane caveolae?, IUBMB Life, vol.55, pp.33-35, 2003.

*. Acog, Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists, Hypertension in pregnancy. Number, vol.219, issue.91, pp.175-183, 1986.

H. Acosta-sison, The relationship of hydatidiform mole to pre-eclampsia and eclampsia, American Journal of Obstetrics and Gynecology, vol.71, pp.1279-1282, 1956.

A. Aitio, UDPglucuronosyltransferase of the human placenta, Biochem. Pharmacol, vol.23, pp.2203-2205, 1974.

K. G. *alberti, P. Zimmet, and J. Shaw, Metabolic syndrome--a new worldwide definition. A Consensus Statement from the International Diabetes Federation, Diabet. Med, vol.23, pp.469-480, 2006.

V. Albiñana, M. P. Zafra, J. Colau, R. Zarrabeitia, L. Recio-poveda et al., Mutation affecting the proximal promoter of Endoglin as the origin of hereditary hemorrhagic telangiectasia type 1, BMC Med. Genet, vol.18, p.20, 2017.

E. D. Albrecht, P. , and G. J. , Placental steroid hormone biosynthesis in primate pregnancy, Endocr. Rev, vol.11, pp.124-150, 1990.

M. Altomonte, R. Montagner, E. Fonsatti, F. Colizzi, I. Cattarossi et al., Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma, Br. J. Cancer, vol.74, pp.1586-1591, 1996.

A. Alvarez, C. Hermenegildo, A. C. Issekutz, J. V. Esplugues, and M. Sanz, , 2002.

, Estrogens inhibit angiotensin II-induced leukocyte-endothelial cell interactions in vivo via rapid endothelial nitric oxide synthase and cyclooxygenase activation, Circ. Res, vol.91, pp.1142-1150

R. Amarasekara, R. W. Jayasekara, H. Senanayake, and V. H. Dissanayake, , 2015.

, Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia, J. Obstet. Gynaecol. Res, vol.41, pp.662-669

G. *american-college-of-obstetricians, Hypertension in pregnancy, 2013.

G. *american-college-of-obstetricians, Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy, Obstet Gynecol, vol.122, pp.1122-1131, 2013.

, Diagnosis and classification of diabetes mellitus, Diabetes Care, vol.27, issue.1, pp.5-10, 2004.

H. M. Arthur, J. Ure, A. J. Smith, G. Renforth, D. I. Wilson et al., Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development, Dev. Biol, vol.217, pp.42-53, 2000.

J. Arts, G. G. Kuiper, J. M. Janssen, J. A. Gustafsson, C. W. Löwik et al., Differential expression of estrogen receptors alpha and beta mRNA during differentiation of human osteoblast SV-HFO cells, Endocrinology, vol.138, pp.5067-5070, 1997.

L. M. *askie, L. Duley, D. J. Henderson-smart, L. A. Stewart, . Paris-collaborative et al., Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data, Lancet, vol.369, pp.1791-1798, 2007.

O. Avallet, M. Vigier, P. Leduque, P. M. Dubois, and J. M. Saez, Expression and regulation of transforming growth factor-beta 1 messenger ribonucleic acid and protein in cultured porcine Leydig and Sertoli cells, Endocrinology, vol.134, pp.2079-2087, 1994.
URL : https://hal.archives-ouvertes.fr/hal-02705861

Z. Badran, X. Struillou, C. Verner, T. Clee, M. Rakic et al., Periodontitis as a risk factor for systemic disease: Are microparticles the missing link?, Med. Hypotheses, vol.84, pp.555-556, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01392489

N. P. Barbara, J. L. Wrana, and M. Letarte, Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily, J. Biol. Chem, vol.274, pp.584-594, 1999.

E. R. Barnea, N. J. Maclusky, and F. Naftolin, Kinetics of catechol estrogenestrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity, Steroids, vol.41, pp.643-656, 1983.

M. P. Barr, A. M. Byrne, A. M. Duffy, C. M. Condron, M. Devocelle et al., A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells, Br. J. Cancer, vol.92, pp.328-333, 2005.

P. Bausero, M. Ben-mahdi, J. Mazucatelli, C. Bloy, and M. Perrot-applanat, , 2000.

, Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia, Am. J. Physiol. Heart Circ. Physiol, vol.279, pp.2033-2042

Y. Bdolah, C. Lam, A. Rajakumar, V. Shivalingappa, W. Mutter et al., Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia?, American Journal of Obstetrics and Gynecology, vol.198, pp.1-428, 2008.

Y. Bdolah, U. Elchalal, S. Natanson-yaron, H. Yechiam, T. Bdolah-abram et al., , 2014.

, Relationship between nulliparity and preeclampsia may be explained by altered circulating soluble fms-like tyrosine kinase 1, Hypertens Pregnancy, vol.33, pp.250-259

M. Beato and J. Klug, Steroid hormone receptors: an update, Hum. Reprod. Update, vol.6, pp.225-236, 2000.

M. Beaufils, Pré-éclampsie et risque cardiovasculaire ultérieur, La Revue de Médecine Interne, vol.32, pp.36-40, 2011.

M. Beaufils, S. Uzan, R. Donsimoni, and J. C. Colau, Prevention of pre-eclampsia by early antiplatelet therapy, Lancet, vol.1, pp.840-842, 1985.

T. Bellón, A. Corbí, P. Lastres, C. Calés, M. Cebrián et al., Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions, Eur. J. Immunol, vol.23, pp.2340-2345, 1993.

A. H. Berg and P. E. Scherer, Adipose tissue, inflammation, and cardiovascular disease, Circ. Res, vol.96, pp.939-949, 2005.

N. Berkane, Définitions et conséquences des hypertensions artérielles de la grossesse, Annales Françaises d'Anesthésie et de Réanimation, vol.29, pp.1-6, 2010.

N. Berkane, P. Liere, J. Oudinet, A. Hertig, G. Lefèvre et al., From pregnancy pregnancy to preeclampsia : a key role for estrogens, Endocr Rev, vol.3, pp.123-144, 2017.

N. Berkane, P. Liere, G. Lefevre, N. Alfaidy, R. A. Nahed et al., Abnormal steroidogenesis and aromatase activity in preeclampsia, Placenta, vol.69, pp.40-49, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02384945

N. Berkane, P. Liere, G. Lefevre, N. Alfaidy, R. A. Nahed et al., Abnormal steroidogenesis and aromatse activity in preeclampsia, Placenta, vol.69, pp.40-49, 2018.

S. Berndt, S. Blacher, C. Munaut, J. Detilleux, S. Perrier-d'hauterive et al., Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-? receptor activation, The FASEB Journal, vol.27, pp.1309-1321, 2013.

S. Bharadwaj, B. Vishnu-bhat, B. Adhisivam, Z. Bobby, S. et al., , 2017.

, Oxidative stress in preeclamptic mother -newborn dyads and its correlation with early neonatal outcome -a case control study, J. Matern. Fetal. Neonatal. Med, pp.1-16

R. S. Bhaskaran, A. , and M. , The post-endocytotic fate of the gonadotropin receptors is an important determinant of the desensitization of gonadotropin responses, J. Mol. Endocrinol, vol.34, pp.447-457, 2005.

C. H. Blomquist, Kinetic analysis of enzymic activities: prediction of multiple forms of 17 beta-hydroxysteroid dehydrogenase, J. Steroid Biochem. Mol. Biol, vol.55, pp.515-524, 1995.

C. A. Boocock, D. S. Charnock-jones, A. M. Sharkey, J. Mclaren, P. J. Barker et al., Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma, J. Natl. Cancer Inst, vol.87, pp.506-516, 1995.

M. B. Boroujeni, N. B. Boroujeni, and M. Gholami, The effect of progesterone treatment after ovarian induction on endometrial VEGF gene expression and its receptors in mice at pre-implantation time, Iran J Basic Med Sci, vol.19, pp.252-257, 2016.

P. C. Brittain and P. Bayliss, Partial hydatidiform molar pregnancy presenting with severe preeclampsia prior to twenty weeks gestation: a case report and review of the literature, Mil Med, vol.160, pp.42-44, 1995.

S. Brouillet, P. Murthi, P. Hoffmann, A. Salomon, F. Sergent et al., EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR), Cell. Mol. Life Sci, vol.70, pp.511-525, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01234897

F. C. Brownfoot, S. Tong, N. J. Hannan, N. K. Binder, S. P. Walker et al., Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia, vol.66, pp.687-697, 2015.

S. E. Bulun, Aromatase and estrogen receptor ? deficiency, Fertil. Steril, vol.101, pp.323-329, 2014.

G. Bunone, P. A. Briand, R. J. Miksicek, and D. Picard, Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation, EMBO J, vol.15, pp.2174-2183, 1996.

G. J. Burton, H. Yung, T. Cindrova-davies, C. , and D. S. , , 2009.

, Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia, Placenta, vol.30, pp.43-48

S. Bussen and D. Bussen, Influence of the vascular endothelial growth factor on the development of severe pre-eclampsia or HELLP syndrome, Arch. Gynecol. Obstet, vol.284, pp.551-557, 2011.

M. De-caestecker, The transforming growth factor-beta superfamily of receptors, Cytokine Growth Factor Rev, vol.15, pp.1-11, 2004.

I. Caniggia, C. V. Taylor, J. W. Ritchie, S. J. Lye, and M. Letarte, Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants, Endocrinology, vol.138, pp.4977-4988, 1997.

P. Carmeliet, L. Moons, A. Luttun, V. Vincenti, V. Compernolle et al., Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions, Nat. Med, vol.7, pp.575-583, 2001.

A. M. Carter, Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders, Reproduction, vol.141, pp.391-396, 2011.

A. M. Carter, A. C. Enders, and R. Pijnenborg, The role of invasive trophoblast in implantation and placentation of primates, Philos. Trans. R. Soc. Lond., B, Biol. Sci, vol.370, 2015.

V. D. Castracane and J. W. Goldzieher, Timing of the luteal-placental shift in the baboon (Papio cynocephalus), Endocrinology, vol.118, pp.506-512, 1986.

,. *challier and S. Uzan, , 2003.

, Med Sci (Paris), vol.19, pp.1111-1120

K. L. Chambliss and P. W. Shaul, Estrogen modulation of endothelial nitric oxide synthase, Endocr. Rev, vol.23, pp.665-686, 2002.

S. Chandra, H. Scott, L. Dodds, C. Watts, C. Blight et al., Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes, Am. J. Obstet. Gynecol, vol.189, pp.775-781, 2003.

S. P. Chauhan, L. M. Gupta, N. W. Hendrix, and V. Berghella, Intrauterine growth restriction: comparison of American College of Obstetricians and Gynecologists practice bulletin with other national guidelines, American Journal of Obstetrics and Gynecology, vol.409, pp.1-409, 0200.

S. Cheifetz and J. Massagué, Isoform-specific transforming growth factor-beta binding proteins with membrane attachments sensitive to phosphatidylinositol-specific phospholipase C, J. Biol. Chem, vol.266, pp.20767-20772, 1991.

S. Cheifetz, T. Bellón, C. Calés, S. Vera, C. Bernabeu et al., Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells, J. Biol. Chem, vol.267, pp.19027-19030, 1992.

C. Chen, C. Chen, Y. Yang, T. Su, C. et al., Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia, Placenta, vol.25, pp.413-421, 2004.

G. Chen, . Wilson, S. H. Wang, H. Z. Zheng, J. J. Walker et al., Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in preeclampsia, Clin. Exp. Immunol, vol.104, pp.154-159, 1996.

M. Chiang, F. Liang, C. Chen, C. Chang, M. Cheong et al., Mechanism of hypoxia-induced GCM1 204 degradation: implications for the pathogenesis of preeclampsia, J. Biol. Chem, vol.284, pp.17411-17419, 2009.

J. Choi and J. Smitz, Luteinizing hormone and human chorionic gonadotropin: Origins of difference, Molecular and Cellular Endocrinology, vol.383, pp.203-213, 2014.

I. Choi, C. Ko, O. K. Park-sarge, R. Nie, R. A. Hess et al., Human estrogen receptor beta-specific monoclonal antibodies: characterization and use in studies of estrogen receptor beta protein expression in reproductive tissues, Mol. Cell. Endocrinol, vol.181, pp.139-150, 2001.

H. W. Christinger, G. Fuh, A. M. De-vos, and C. Wiesmann, The Crystal Structure of Placental Growth Factor in Complex with Domain 2 of Vascular Endothelial Growth Factor Receptor-1, Journal of Biological Chemistry, vol.279, pp.10382-10388, 2004.

D. E. Clark, S. K. Smith, A. M. Sharkey, C. , and D. S. , Localization of VEGF and expression of its receptors flt and KDR in human placenta throughout pregnancy, Hum. Reprod, vol.11, pp.1090-1098, 1996.

D. E. Clark, S. K. Smith, Y. He, K. A. Day, D. R. Licence et al., CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose, Aspirin Study in Pregnancy) Collaborative Group. Lancet, vol.59, pp.619-629, 1994.

W. H. Clewell, B. A. Carson, and G. Meschia, Comparison of uterotrophic and vascular effects of estradiol-17beta and estriol in the mature organism, Am. J. Obstet. Gynecol, vol.129, pp.384-388, 1977.

S. Cnattingius and M. L. Nordström, Maternal smoking and feto-infant mortality: biological pathways and public health significance, Acta Paediatr, vol.85, pp.1400-1402, 1996.

*. Conde-agudelo, A. Althabe, F. Belizán, J. M. Kafury-goeta, and A. C. , Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review, Am. J. Obstet. Gynecol, vol.181, pp.1026-1035, 1999.

J. C. Condon, D. B. Hardy, K. Kovaric, and C. R. Mendelson, Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function, Mol. Endocrinol, vol.20, pp.764-775, 2006.

M. Coolman, S. Timmermans, C. J. De-groot, H. Russcher, J. Lindemans et al., , 2012.

, Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes, Obstet Gynecol, vol.119, pp.1190-1200

J. J. Corcoran, C. Nicholson, M. Sweeney, J. C. Charnock, S. C. Robson et al., Human uterine and placental arteries exhibit tissue-specific acute 205 responses to 17?-estradiol and estrogen-receptor-specific agonists, Mol. Hum. Reprod, vol.20, pp.433-441, 2014.

D. C. Cornelius, Preeclampsia: From Inflammation to Immunoregulation, Clin Med Insights Blood Disord, vol.11, pp.1179545-17752325, 2018.

R. Coya, P. Martul, J. Algorta, M. A. Aniel-quiroga, M. A. Busturia et al.,

I. M. Craici, S. J. Wagner, K. R. Bailey, P. D. Fitz-gibbon, C. M. Wood-wentz et al., Podocyturia Predates Proteinuria and Clinical Features of Preeclampsia: Longitudinal Prospective Study, vol.61, pp.1289-1296, 2013.

H. S. *cuckle, Screening for pre-eclampsia--lessons from aneuploidy screening, Placenta, vol.32, pp.42-48, 2011.

M. J. Cudmore, P. W. Hewett, S. Ahmad, K. Wang, M. Cai et al., The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis, Nat Commun, vol.3, p.972, 2012.

A. L. Er, Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative, Archives of Internal Medicine, vol.172, p.144, 2012.

G. R. Cunningham, D. J. Tindall, T. J. Lobl, J. A. Campbell, and A. R. Means, Steroid structural requirements for high affinity binding to human sex steroid binding protein (SBP), Steroids, vol.38, pp.243-262, 1981.

D. J. Darkow, L. Lu, and R. E. White, Estrogen relaxation of coronary artery smooth muscle is mediated by nitric oxide and cGMP, Am. J. Physiol, vol.272, pp.2765-2773, 1997.

S. K. Das, J. Tan, D. C. Johnson, and S. K. Dey, Differential spatiotemporal regulation of lactoferrin and progesterone receptor genes in the mouse uterus by primary estrogen, catechol estrogen, and xenoestrogen, Endocrinology, vol.139, pp.2905-2915, 1998.

J. M. Davison, V. Homuth, A. Jeyabalan, K. P. Conrad, S. A. Karumanchi et al., New aspects in the pathophysiology of preeclampsia, J. Am. Soc. Nephrol, vol.15, pp.2440-2448, 2004.

G. *desoye and S. Hauguel-de-mouzon, The human placenta in gestational diabetes mellitus. The insulin and cytokine network, Diabetes Care, vol.30, issue.2, pp.120-126, 2007.

S. Dimmeler, I. Fleming, B. Fisslthaler, C. Hermann, R. Busse et al., Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation, Nature, vol.399, pp.601-605, 1999.

R. Drolet, M. Simard, J. Plante, P. Laberge, and Y. Tremblay, Human type 2 17 beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy, Reprod. Biol. Endocrinol, vol.5, p.30, 2007.

G. E. Dressing, J. E. Goldberg, N. J. Charles, K. L. Schwertfeger, and C. A. Lange, Membrane progesterone receptor expression in mammalian tissues: A review of regulation and physiological implications, Steroids, vol.76, pp.11-17, 2011.

R. *druckmann and M. Druckmann, Progesterone and the immunology of pregnancy, The Journal of Steroid Biochemistry and Molecular Biology, vol.97, pp.389-396, 2005.

R. Dubroff, Cholesterol confusion and statin controversy, World Journal of Cardiology, vol.7, p.404, 2015.

S. E. Elliott, N. F. Parchim, R. E. Kellems, Y. Xia, A. R. Soffici et al., A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50, Clin. Immunol, vol.168, pp.64-71, 2016.

F. A. English, L. C. Kenny, and F. P. Mccarthy, Risk factors and effective management of preeclampsia, Integr Blood Press Control, vol.8, pp.7-12, 2015.

M. Epiney, P. Ribaux, P. Arboit, O. Irion, and M. Cohen, Comparative analysis of secreted proteins from normal and preeclamptic trophoblastic cells using proteomic approaches, J Proteomics, vol.75, pp.1771-1777, 2012.

J. Evans, Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor, American Journal of Reproductive Immunology, vol.75, pp.333-340, 2016.

J. J. Evans, I. L. Sin, G. B. Duff, and C. M. Frampton, Estrogen-induced transcortin increase and progesterone and cortisol interactions: implications from pregnancy studies, Ann. Clin. Lab. Sci, vol.17, pp.101-105, 1987.

J. N. Fain, Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells, Vitam. Horm, vol.74, pp.443-477, 2006.

C. N. Falany, J. Wheeler, T. S. Oh, and J. L. Falany, Steroid sulfation by expressed human cytosolic sulfotransferases, J. Steroid Biochem. Mol. Biol, vol.48, pp.369-375, 1994.

M. S. Fernandes, Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues, Journal of Endocrinology, vol.187, pp.89-101, 2005.

E. Fernández-ruiz, S. St-jacques, T. Bellón, M. Letarte, and C. Bernabéu, Assignment of the human endoglin gene (END) to 9q34-->qter, Cytogenet. Cell Genet, vol.64, pp.204-207, 1993.

E. Filardo, J. Quinn, Y. Pang, C. Graeber, S. Shaw et al., Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane, Endocrinology, vol.148, pp.3236-3245, 2007.

E. J. Filardo, J. A. Quinn, K. I. Bland, and A. R. Frackelton, Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF, Mol. Endocrinol, vol.14, pp.1649-1660, 2000.

E. J. Filardo, J. A. Quinn, A. R. Frackelton, and K. I. Bland, Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis, Mol. Endocrinol, vol.16, pp.70-84, 2002.

M. Fischer and E. Schmutzhard, Posterior reversible encephalopathy syndrome, J. Neurol, vol.264, pp.1608-1616, 2017.

C. Fischer, M. Mazzone, B. Jonckx, and P. Carmeliet, FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?, Nat. Rev. Cancer, vol.8, pp.942-956, 2008.

K. M. Flegal, M. D. Carroll, C. L. Ogden, and L. R. Curtin, Prevalence and trends in obesity among US adults, JAMA, vol.303, pp.235-241, 1999.

P. Florio, A. Imperatore, F. Sanseverino, M. Torricelli, F. M. Reis et al., The measurement of maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein improves the early prediction of preeclampsia, J. Clin. Endocrinol. Metab, vol.89, pp.4673-4677, 2004.

T. Flötotto, D. Niederacher, D. Hohmann, T. Heimerzheim, P. Dall et al., Molecular mechanism of estrogen receptor (ER)alpha-specific, estradiol-dependent expression of the progesterone receptor (PR) Bisoform, J. Steroid Biochem. Mol. Biol, vol.88, pp.131-142, 2004.

J. M. Foidart, J. Hustin, M. Dubois, and J. P. Schaaps, The human placenta becomes haemochorial at the 13th week of pregnancy, Int. J. Dev. Biol, vol.36, pp.451-453, 1992.

G. H. Fong, J. Rossant, M. Gertsenstein, and M. L. Breitman, Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium, Nature, vol.376, pp.66-70, 1995.

C. Förster, S. Mäkela, A. Wärri, S. Kietz, D. Becker et al., Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium, Proc. Natl. Acad. Sci. U.S.A, vol.99, pp.15578-15583, 2002.

J. A. Forsythe, B. H. Jiang, N. V. Iyer, F. Agani, S. W. Leung et al., Activation of vascular endothelial growth factor gene transcription by hypoxiainducible factor 1, Mol. Cell. Biol, vol.16, pp.4604-4613, 1996.

G. K. Frampton, J. Jones, M. Rose, and L. Payne, Placental growth factor (alone or in combination with soluble fms-like tyrosine kinase 1) as an aid to the assessment of women with suspected pre-eclampsia: systematic review and economic analysis, Health Technology Assessment, vol.20, pp.1-160, 2016.

A. Furcron, R. Romero, T. N. Mial, A. Balancio, B. Panaitescu et al., Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1, Biology of Reproduction, vol.94, 2016.

T. Fushima, A. Sekimoto, T. Minato, T. Ito, Y. Oe et al., Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice, PLOS ONE, vol.11, 2016.

N. *gamage, A. Barnett, N. Hempel, R. G. Duggleby, K. F. Windmill et al., Human sulfotransferases and their role in chemical metabolism, Toxicol. Sci, vol.90, pp.5-22, 2006.

C. E. Gargett, M. Zaitseva, K. Bucak, S. Chu, P. J. Fuller et al., 17Beta-estradiol up-regulates vascular endothelial growth factor receptor-2 expression in human myometrial microvascular endothelial cells: role of estrogen receptor-alpha and -beta, J. Clin. Endocrinol. Metab, vol.87, pp.4341-4349, 2002.

L. Ghulmiyyah and B. Sibai, Maternal mortality from preeclampsia/eclampsia, Semin. Perinatol, vol.36, pp.56-59, 2012.

P. H. Giangrande and D. P. Mcdonnell, The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene, Recent Prog. Horm. Res, vol.54, pp.313-314, 1999.

H. Gille, J. Kowalski, B. Li, J. Lecouter, B. Moffat et al., Analysis of Biological Effects and Signaling Properties of Flt-1, 2001.

, KDR (VEGFR-2): A reassement using novel receptor-specific vascular endothelial growth factormutants, Journal of Biological Chemistry, vol.276, pp.3222-3230

G. Ginsberg and D. C. Rice, Does rapid metabolism ensure negligible risk from bisphenol A?, Environ. Health Perspect, vol.117, pp.1639-1643, 2009.

R. Giordano, A. Cacciatore, M. Romano, B. La-rosa, I. Fonti et al., , 2010.

, Uterine artery Doppler flow studies in obstetric practice, J Prenat Med, vol.4, pp.59-62

F. Girdler and I. Brotherick, The oestrogen receptors (ER alpha and ER beta) and their role in breast cancer: a review, Breast, vol.9, pp.194-200, 2000.

F. Goffinet, D. Aboulker, J. Paris-llado, M. Bucourt, M. Uzan et al., Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results: a multicenter randomised controlled trial, BJOG, vol.108, pp.510-518, 2001.

S. Goldman and E. Shalev, Progesterone receptor isoforms profile, modulate matrix metalloproteinase 2 expression in the decidua, Am. J. Obstet. Gynecol, vol.197, pp.1-8, 2007.

*. Goldman-wohl, D. , Y. , and S. , Regulation of trophoblast invasion: from normal implantation to pre-eclampsia, Mol. Cell. Endocrinol, vol.187, pp.233-238, 2002.

A. Gougos and M. Letarte, Identification of a human endothelial cell antigen with monoclonal antibody 44G4 produced against a pre-B leukemic cell line, J. Immunol, vol.141, pp.1925-1933, 1988.

A. Gougos, S. St-jacques, A. Greaves, P. J. O'connell, A. J. Apice et al., Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts, Int. Immunol, vol.4, pp.83-92, 1992.

C. J. Green, P. Lichtlen, N. T. Huynh, M. Yanovsky, K. R. Laderoute et al., Placenta growth factor gene expression is induced by hypoxia in fibroblasts: a central role for metal transcription factor-1, Cancer Res, vol.61, pp.2696-2703, 2001.

S. Green, P. Walter, V. Kumar, A. Krust, J. M. Bornert et al., Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A, Nature, vol.320, pp.134-139, 1986.

K. M. Groom, W. Ganzevoort, Z. Alfirevic, K. Lim, A. T. Papageorghiou et al., Clinicians should stop prescribing sildenafil for fetal growth restriction (FGR): comment from the STRIDER Consortium: Physician Alert, Ultrasound in Obstetrics & Gynecology, 2018.

C. J. Gruber, W. Tschugguel, C. Schneeberger, and J. C. Huber, Production and actions of estrogens, N. Engl. J. Med, vol.346, pp.340-352, 2002.

P. Grzesik, A. Kreuchwig, C. Rutz, J. Furkert, B. Wiesner et al., Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region, Frontiers in Endocrinology, 2015.

J. Guibourdenche, K. Handschuh, V. Tsatsaris, P. Gerbaud, M. C. Leguy et al., Hyperglycosylated hCG Is a Marker of Early Human Trophoblast Invasion, The Journal of Clinical Endocrinology & Metabolism, vol.95, pp.240-244, 2010.

H. C. Guldberg and C. A. Marsden, Catechol-O-methyl transferase: pharmacological aspects and physiological role, Pharmacol. Rev, vol.27, pp.135-206, 1975.

E. Gurpide, C. Marks, D. De-ziegler, P. D. Berk, and J. M. Brandes, Asymmetric release of estrone and estradiol derived from labeled precursors in perfused human placentas, Am. J. Obstet. Gynecol, vol.144, pp.551-555, 1982.

J. A. *gustafsson, Estrogen receptor beta--a new dimension in estrogen mechanism of action, J. Endocrinol, vol.163, pp.379-383, 1999.

J. A. *gustafsson and M. Warner, Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer, J. Steroid Biochem. Mol. Biol, vol.74, pp.245-248, 2000.

B. Haddad, N. Winer, Y. Chitrit, V. Houfflin-debarge, C. Chauleur et al., Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications: A Randomized Controlled Trial, Obstet Gynecol, vol.128, pp.1053-1063, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01900637

C. L. Haggerty, I. Panum, S. A. Uldum, D. C. Bass, J. Olsen et al., Chlamydia trachomatis infection may increase the risk of preeclampsia, Pregnancy Hypertens, vol.3, pp.28-33, 2013.

S. Haider and M. Knöfler, Human Tumour Necrosis Factor: Physiological and Pathological Roles in Placenta and Endometrium, Placenta, vol.30, pp.111-123, 2009.

G. L. Hammond, Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action, Journal of Endocrinology, vol.230, pp.13-25, 2016.

G. L. Hammond, K. N. Hogeveen, M. Visser, C. Bennink, and H. J. , Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells, Climacteric, vol.11, pp.41-46, 2008.

D. J. *handelsman and L. Wartofsky, Requirement for mass spectrometry sex steroid assays in the, Journal of Clinical Endocrinology and Metabolism. J. Clin. Endocrinol. Metab, vol.98, pp.3971-3973, 2013.

K. Handschuh, J. Guibourdenche, V. Tsatsaris, M. Guesnon, I. Laurendeau et al., Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells, Placenta, vol.28, pp.175-184, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00000052

I. Hanukoglu, Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis, J. Steroid Biochem. Mol. Biol, vol.43, pp.779-804, 1992.

M. Harris, Monoclonal antibodies as therapeutic agents for cancer, Lancet Oncol, vol.5, pp.292-302, 2004.

Y. He, S. K. Smith, K. A. Day, D. E. Clark, D. R. Licence et al.,

, Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity, Mol. Endocrinol, vol.13, pp.537-545

F. R. Helmo, F. L. De-castro, R. M. Etchebehere, M. Reis, J. R. Machado et al., 12 Expression of corticotropin-releasing hormone in the placentas of pregnant women with hypertensive disorders. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, vol.6, pp.183-184, 2016.

A. Hennessy, A. G. Gillin, D. M. Painter, P. J. Kirwan, J. F. Thompson et al., Evidence for Preeclampsia in a Baboon Pregnancy with Twins, Hypertension in Pregnancy, vol.16, pp.223-228, 1997.

A. Hertig, N. Berkane, G. Lefevre, K. Toumi, H. Marti et al., Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia, Clin. Chem, vol.50, pp.1702-1703, 2004.

A. Hertig, G. Lefevre, K. Toumi, E. Rondeau, J. Capeau et al.,

, Soluble endoglin levels during normotensive and hypertensive pregnancies, Eur. J. Obstet. Gynecol. Reprod. Biol, vol.140, pp.138-140

A. Hertig, P. Liere, N. Chabbert-buffet, J. Fort, A. Pianos et al., Steroid profiling in preeclamptic women: evidence for aromatase deficiency, Am. J. Obstet. Gynecol, vol.203, pp.1-9, 2010.

M. A. Hervé, G. Meduri, F. G. Petit, T. S. Domet, G. Lazennec et al., Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus, J. Endocrinol, vol.188, pp.91-99, 2006.

K. Heussner, M. Ruebner, H. Huebner, W. Rascher, C. Menendez-castro et al., Species differences of 11beta-hydroxysteroid dehydrogenase type 2 function in human and rat term placenta determined via LC-MS/MS, Placenta, vol.37, pp.79-84, 2016.

U. Hiden, A. Maier, M. Bilban, N. Ghaffari-tabrizi, C. Wadsack et al., Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy, Diabetologia, vol.49, pp.123-131, 2006.

L. Higgins, T. A. Mills, S. L. Greenwood, E. J. Cowley, C. P. Sibley et al., Maternal obesity and its effect on placental cell turnover, J. Matern. Fetal. Neonatal. Med, vol.26, pp.783-788, 2013.

M. Hill, A. Pa?ízek, D. Cibula, R. Kancheva, J. E. Jirásek et al., Steroid metabolome in fetal and maternal body fluids in human late pregnancy, J. Steroid Biochem. Mol. Biol, vol.122, pp.114-132, 2010.

M. Hill, A. Parízek, J. E. Jirásek, M. Jirkovská, M. Velíková et al., Is maternal progesterone actually independent of the fetal steroids, Physiol Res, vol.59, pp.211-224, 2010.

S. Hiratsuka, K. Nakao, K. Nakamura, M. Katsuki, Y. Maru et al., , 2005.

, Membrane Fixation of Vascular Endothelial Growth Factor Receptor 1 Ligand-Binding Domain Is Important for Vasculogenesis and Angiogenesis in Mice, Molecular and Cellular Biology, vol.25, pp.346-354

K. Hisamoto, M. Ohmichi, H. Kurachi, J. Hayakawa, Y. Kanda et al., Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells, J. Biol. Chem, vol.276, pp.3459-3467, 2001.

J. T. Ho, J. G. Lewis, P. O'loughlin, C. J. Bagley, R. Romero et al., Reduced maternal corticosteroid-binding globulin and cortisol levels in preeclampsia and gamete recipient pregnancies, Clin. Endocrinol. (Oxf), vol.66, pp.869-877, 2007.

A. *hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van-oosterom et al., Vascular endothelial growth factor and angiogenesis, Pharmacol. Rev, vol.56, pp.549-580, 2004.

K. Hogg, J. D. Blair, D. E. Mcfadden, P. Von-dadelszen, and W. P. Robinson, Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta, PLoS ONE, vol.8, 2013.

C. F. Holinka, E. Diczfalusy, C. Bennink, and H. J. , Estetrol: a unique steroid in human pregnancy, J. Steroid Biochem. Mol. Biol, vol.110, pp.138-143, 2008.

D. I. Holmes, Z. , and I. , Placental growth factor induces FosB and c-Fos gene expression via Flt-1 receptors, FEBS Lett, vol.557, pp.93-98, 2004.

H. H. Hou, S. L. Cheng, H. T. Liu, F. Z. Yang, H. C. Wang et al., Elastase induced lung epithelial cell apoptosis and emphysema through placenta growth factor, Cell Death Dis, vol.4, p.793, 2013.

T. Hung, J. N. Skepper, D. S. Charnock-jones, and G. J. Burton, Hypoxiareoxygenation: a potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia, Circ. Res, vol.90, pp.1274-1281, 2002.

J. A. *hutcheon, S. Lisonkova, J. , and K. S. , Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy, Best Practice & Research Clinical Obstetrics & Gynaecology, vol.25, pp.391-403, 2011.

O. Ishibashi, A. Ohkuchi, M. M. Ali, R. Kurashina, S. Luo et al., , 2012.

, dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia, Hypertension, vol.59, pp.265-273

T. Ishida, F. Seo, K. Hirato, T. Fukuda, T. Yanaihara et al.,

, Nippon Sanka Fujinka Gakkai Zasshi, vol.37, pp.547-554

D. Islami, P. Bischof, and D. Chardonnens, Modulation of placental vascular endothelial growth factor by leptin and hCG, Mol. Hum. Reprod, vol.9, pp.395-398, 2003.

E. Jauniaux, J. Zaidi, D. Jurkovic, S. Campbell, and J. Hustin, Comparison of colour Doppler features and pathological findings in complicated early pregnancy, Hum. Reprod, vol.9, pp.2432-2437, 1994.

W. *-jelkmann, Pitfalls in the measurement of circulating vascular endothelial growth factor, Clin. Chem, vol.47, pp.617-623, 2001.

A. Jeyabalan, R. W. Powers, A. R. Durica, G. F. Harger, J. M. Roberts et al., Cigarette Smoke Exposure and Angiogenic Factors in Pregnancy and Preeclampsia, American Journal of Hypertension, vol.21, pp.943-947, 2008.

B. Jiang and C. R. Mendelson, USF1 and USF2 mediate inhibition of human trophoblast differentiation and CYP19 gene expression by Mash-2 and hypoxia, Mol. Cell. Biol, vol.23, pp.6117-6128, 2003.

D. W. Johnson, J. N. Berg, M. A. Baldwin, C. J. Gallione, I. Marondel et al., Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2, Nat. Genet, vol.13, pp.189-195, 1996.

C. Jung, J. T. Ho, D. J. Torpy, A. Rogers, M. Doogue et al., A Longitudinal Study of Plasma and Urinary Cortisol in Pregnancy and Postpartum, The Journal of Clinical Endocrinology & Metabolism, vol.96, pp.1533-1540, 2011.

T. J. Kaitu'u-lino, K. R. Palmer, C. L. Whitehead, E. Williams, M. Lappas et al., MMP-14 Is Expressed in Preeclamptic Placentas and Mediates Release of Soluble Endoglin, The American Journal of Pathology, vol.180, pp.888-894, 2012.

C. B. *kallen, Steroid hormone synthesis in pregnancy, Obstet. Gynecol. Clin. North Am, vol.31, pp.795-816, 2004.

J. Kaludjerovic and W. E. Ward, The Interplay between Estrogen and Fetal Adrenal Cortex, J Nutr Metab, p.837901, 2012.

K. Kaul, M. Apostolopoulou, and M. Roden, Insulin resistance in type 1 diabetes mellitus, Metab. Clin. Exp, vol.64, pp.1629-1639, 2015.

R. L. Kendall and K. A. Thomas, Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor, Proc. Natl. Acad. Sci. U.S.A, vol.90, pp.10705-10709, 1993.

R. L. Kendall, G. Wang, and K. A. Thomas, Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR, Biochem. Biophys. Res. Commun, vol.226, pp.324-328, 1996.

P. A. Kern, S. Ranganathan, C. Li, L. Wood, and G. Ranganathan, Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance, Am. J. Physiol. Endocrinol. Metab, vol.280, pp.745-751, 2001.

K. S. Khan, D. Wojdyla, L. Say, A. M. Gülmezoglu, and P. F. Van-look, WHO analysis of causes of maternal death: a systematic review, Lancet, vol.367, pp.1066-1074, 2006.

J. Kim and E. Chapman-davis, Role of Progesterone in Endometrial Cancer, Seminars in Reproductive Medicine, vol.28, pp.81-090, 2010.

J. J. Kim, S. B. Lee, J. K. Park, and Y. D. Yoo, TNF-alpha-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L), Cell Death Differ, vol.17, pp.1420-1434, 2010.

M. Kim, H. J. Park, J. W. Seol, J. Y. Jang, Y. Cho et al., VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy: Uterine angiogenesis and vascular remodelling, EMBO Molecular Medicine, vol.5, pp.1415-1430, 2013.

H. Kimura and H. Esumi, Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis, Acta Biochim. Pol, vol.50, pp.49-59, 2003.

M. A. Klieber, C. Underhill, G. L. Hammond, and Y. A. Muller, Corticosteroidbinding Globulin, a Structural Basis for Steroid Transport and Proteinase-triggered Release, Journal of Biological Chemistry, vol.282, pp.29594-29603, 2007.

M. Knight, C. W. Redman, E. A. Linton, and I. L. Sargent, Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies, Br J Obstet Gynaecol, vol.105, pp.632-640, 1998.

K. Koga, Y. Osuga, O. Yoshino, Y. Hirota, X. Ruimeng et al., Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia, J. Clin. Endocrinol. Metab, vol.88, pp.2348-2351, 2003.

S. Koganti, R. Snyder, U. Gumaste, V. T. Karamyan, and T. Thekkumkara, 2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT(1) receptor, Eur. J. Pharmacol, vol.723, pp.131-140, 2014.

L. E. Kotch, N. V. Iyer, E. Laughner, and G. L. Semenza, Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death, Dev. Biol, vol.209, pp.254-267, 1999.

L. *kragie, Aromatase in primate pregnancy: a review, Endocr. Res, vol.28, pp.121-128, 2002.

M. D. Krasowski, D. Drees, C. S. Morris, J. Maakestad, J. L. Blau et al., Crossreactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction, BMC Clinical Pathology, vol.14, 2014.

E. V. Kuklina, C. Ayala, and W. M. Callaghan, Hypertensive disorders and severe obstetric morbidity in the United States, Obstet Gynecol, vol.113, pp.1299-1306, 2009.

P. Kumar, Y. Luo, C. Tudela, J. M. Alexander, and C. R. Mendelson, The c-Mycregulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation, Mol. Cell. Biol, vol.33, pp.1782-1796, 2013.

R. Kumar, M. N. Zakharov, S. H. Khan, R. Miki, H. Jang et al., The dynamic structure of the estrogen receptor, J Amino Acids, p.812540, 2011.

T. J. Laatikainen, J. M. Pelkonen, and A. K. Pesonen, Steroid concentrations in placenta and fetal membranes at elective caesarean section and after spontaneous labour, Placenta, vol.3, pp.319-324, 1982.

G. M. Lambert-messerlian, H. M. Silver, F. Petraglia, S. Luisi, I. Pezzani et al., Secondtrimester levels of maternal serum human chorionic gonadotropin and inhibin a as predictors of preeclampsia in the third trimester of pregnancy, J. Soc. Gynecol. Investig, vol.7, pp.170-174, 2000.

D. Lanoix, J. St-pierre, A. A. Lacasse, M. Viau, J. Lafond et al., Stability of reference proteins in human placenta: general protein stains are the benchmark, Placenta, vol.33, pp.151-156, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-00818357

D. Lanoix, A. Lacasse, J. St-pierre, S. C. Taylor, M. Ethier-chiasson et al., Quantitative PCR pitfalls: the case of the human placenta, Mol. Biotechnol, vol.52, pp.234-243, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-00818363

P. Lastres, T. Bellon, C. Cabañas, F. Sanchez-madrid, A. Acevedo et al., Regulated expression on human macrophages of endoglin, an Arg-Gly-Asp-containing surface antigen, Eur. J. Immunol, vol.22, pp.393-397, 1992.

A. *lausman and J. Kingdom, Intrauterine growth restriction: screening, diagnosis, and management, J Obstet Gynaecol Can, vol.35, pp.741-748, 2013.

E. Lecarpentier, A. Atallah, J. Guibourdenche, M. Hebert-schuster, S. Vieillefosse et al., Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP-PKA Signaling Pathway, Hypertension, vol.68, pp.1438-1446, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-02472544

Y. Leung, P. Mak, S. Hassan, and S. Ho, Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling, Proc. Natl. Acad. Sci. U.S.A, vol.103, pp.13162-13167, 2006.

R. J. Levine, J. C. Hauth, L. B. Curet, B. M. Sibai, P. M. Catalano et al., Trial of Calcium to Prevent Preeclampsia, New England Journal of Medicine, vol.337, pp.69-77, 1997.

R. J. Levine, S. E. Maynard, C. Qian, K. Lim, L. J. England et al., Circulating angiogenic factors and the risk of preeclampsia, N. Engl. J. Med, vol.350, pp.672-683, 2004.

R. J. Levine, C. Lam, C. Qian, K. F. Yu, S. E. Maynard et al., Soluble endoglin and other circulating antiangiogenic factors in preeclampsia, N. Engl. J. Med, vol.355, pp.992-1005, 2006.

M. Levitz, Y. , and B. K. , Estrogens in pregnancy, Vitam. Horm, vol.35, pp.109-147, 1977.

B. Li, E. E. Sharpe, A. B. Maupin, A. A. Teleron, A. L. Pyle et al., VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization, FASEB J, vol.20, pp.1495-1497, 2006.

C. Li, N. S. Raikwar, M. K. Santillan, D. A. Santillan, and C. P. Thomas, Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclooxygenase 1, Placenta, vol.36, pp.446-453, 2015.

D. Y. Li, L. K. Sorensen, B. S. Brooke, L. D. Urness, E. C. Davis et al., Defective angiogenesis in mice lacking endoglin, Science, vol.284, pp.1534-1537, 1999.

H. Li, B. Gu, Y. Zhang, D. F. Lewis, W. et al., Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta, Placenta, vol.26, pp.210-217, 2005.

P. Licht, H. Fluhr, J. Neuwinger, D. Wallwiener, and L. Wildt, Is human chorionic gonadotropin directly involved in the regulation of human implantation?, Mol. Cell. Endocrinol, vol.269, pp.85-92, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00531900

P. Liere, Y. Akwa, S. Weill-engerer, B. Eychenne, A. Pianos et al., Validation of an analytical procedure to measure trace amounts of neurosteroids in brain tissue by gas chromatography-mass spectrometry, J. Chromatogr. B Biomed. Sci. Appl, vol.739, pp.301-312, 2000.

P. Liere, A. Pianos, B. Eychenne, A. Cambourg, S. Liu et al., Novel lipoidal derivatives of pregnenolone and dehydroepiandrosterone and absence of their sulfated counterparts in rodent brain, J. Lipid Res, vol.45, pp.2287-2302, 2004.

K. Lundström, M. Salminen, A. Jalanko, R. Savolainen, and I. Ulmanen, Cloning and characterization of human placental catechol-O-methyltransferase cDNA, DNA Cell Biol, vol.10, pp.181-189, 1991.

L. Lunghi, M. E. Ferretti, S. Medici, C. Biondi, and F. Vesce, Control of human trophoblast function, Reprod. Biol. Endocrinol, vol.5, p.6, 2007.

C. X. Ma, A. A. Adjei, O. E. Salavaggione, J. Coronel, L. Pelleymounter et al., Human aromatase: gene resequencing and functional genomics, Cancer Res, vol.65, pp.11071-11082, 2005.

Q. Ma, F. Xiong, and L. Zhang, Gestational hypoxia and epigenetic programming of brain development disorders, Drug Discovery Today, vol.19, pp.1883-1896, 2014.

M. Maged, A. Wageh, M. Shams, and A. Elmetwally, Use of sildenafil citrate in cases of intrauterine growth restriction (IUGR); a prospective trial, Taiwan J Obstet Gynecol, vol.57, pp.483-486, 2018.

L. A. Magee, A. Pels, M. Helewa, E. Rey, P. Von-dadelszen et al., Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary, J Obstet Gynaecol Can, vol.36, pp.416-441, 2014.

D. Maglione, V. Guerriero, G. Viglietto, P. Delli-bovi, and M. G. Persico, Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor, Proc. Natl. Acad. Sci. U.S.A, vol.88, pp.9267-9271, 1991.

M. A. Maher, T. M. Sayyed, and N. Elkhouly, Sildenafil Citrate Therapy for Oligohydramnios: A Randomized Controlled Trial, Obstet Gynecol, vol.129, pp.615-620, 2017.

K. Makki, P. Froguel, and I. Wolowczuk, Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines, ISRN Inflammation, pp.1-12, 2013.

A. Makrigiannakis, T. Vrekoussis, E. Zoumakis, S. Kalantaridou, J. et al., The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence, International Journal of Molecular Sciences, vol.18, p.1305, 2017.

M. Maliqueo, B. Echiburú, and N. Crisosto, Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes, Front Physiol, vol.7, p.152, 2016.

S. C. Maness, D. P. Mcdonnell, and K. W. Gaido, Inhibition of androgen receptordependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells, Toxicol. Appl. Pharmacol, vol.151, pp.135-142, 1998.

D. J. Mangelsdorf, C. Thummel, M. Beato, P. Herrlich, G. Schütz et al., The nuclear receptor superfamily: the second decade, Cell, vol.83, pp.835-839, 1995.

M. Marino, A. , and P. , Membrane association of estrogen receptor alpha and beta influences 17beta-estradiol-mediated cancer cell proliferation, Steroids, vol.73, pp.853-858, 2008.

C. C. Marrs and M. M. Costantine, Should We Add Pravastatin to Aspirin for Preeclampsia Prevention in High-risk Women?, Clin Obstet Gynecol, vol.60, pp.161-168, 2017.

C. P. Martucci and J. Fishman, Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion, Endocrinology, vol.105, pp.1288-1292, 1979.

H. Masuyama, H. Nakatsukasa, N. Takamoto, and Y. Hiramatsu, Correlation between Soluble Endoglin, Vascular Endothelial Growth Factor Receptor-1, p.219, 2007.

P. Adipocytokines-in, The Journal of Clinical Endocrinology & Metabolism, vol.92, pp.2672-2679

K. A. Mcallister, K. M. Grogg, D. W. Johnson, C. J. Gallione, M. A. Baldwin et al., Endoglin, a TGFbeta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1, Nat. Genet, vol.8, pp.345-351, 1994.

S. Meher and L. Duley, Progesterone for preventing pre-eclampsia and its complications, Cochrane Database Syst Rev CD006175, 2006.

S. Meher, L. Duley, K. Hunter, A. , and L. , Antiplatelet therapy before or after 16 weeks' gestation for preventing preeclampsia: an individual participant data meta-analysis, Am. J. Obstet. Gynecol, vol.216, pp.121-128, 2017.

D. Menendez, A. Inga, J. Snipe, O. Krysiak, G. Schönfelder et al., A single-nucleotide polymorphism in a half-binding site creates p53 and estrogen receptor control of vascular endothelial growth factor receptor 1, Mol. Cell. Biol, vol.27, pp.2590-2600, 2007.

K. *miehle, H. Stepan, and M. Fasshauer, Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia, Clin. Endocrinol. (Oxf), vol.76, pp.2-11, 2012.

P. Merviel, J. C. Challier, L. Carbillon, J. M. Foidart, and S. Uzan, The role of integrins in human embryo implantation, Fetal. Diagn. Ther, vol.16, pp.364-371, 2001.

B. Millauer, S. Wizigmann-voos, H. Schnürch, R. Martinez, N. P. Møller et al., High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis, Cell, vol.72, pp.835-846, 1993.

V. M. Miller and S. P. Duckles, Vascular actions of estrogens: functional implications, Pharmacol. Rev, vol.60, pp.210-241, 2008.

W. L. Miller and R. J. Auchus, The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders, Endocrine Reviews, vol.32, pp.81-151, 2011.

F. Milne, C. Redman, J. Walker, P. Baker, J. Bradley et al., The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre-eclampsia in the community, BMJ, vol.330, pp.576-580, 2005.

M. Misrahi, I. Beau, N. Ghinea, B. Vannier, H. Loosfelt et al., The LH/CG and FSH receptors: different molecular forms and intracellular traffic, Mol. Cell. Endocrinol, vol.125, pp.161-167, 1996.

F. Modugno, R. Laskey, A. L. Smith, C. L. Andersen, P. Haluska et al., Hormone response in ovarian cancer: time to reconsider as a clinical target, Endocrine Related Cancer, vol.19, pp.255-279, 2012.

N. Moghrabi, J. R. Head, A. , and S. , Cell type-specific expression of 17 betahydroxysteroid dehydrogenase type 2 in human placenta and fetal liver, J. Clin. Endocrinol. Metab, vol.82, pp.3872-3878, 1997.

S. Montgomery, L. Shaw, N. Pantelides, M. Taggart, A. et al., Acute effects of oestrogen receptor subtype-specific agonists on vascular contractility, Br. J. Pharmacol, vol.139, pp.1249-1253, 2003.

M. Simas, T. A. Crawford, S. L. Bathgate, S. Yan, J. Robidoux et al., Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women, J. Matern. Fetal. Neonatal. Med, vol.27, pp.1038-1048, 2014.

G. Mor, W. Yue, R. J. Santen, L. Gutierrez, M. Eliza et al., Macrophages, estrogen and the microenvironment of breast cancer, J. Steroid Biochem. Mol. Biol, vol.67, pp.403-411, 1998.

Y. Morel, F. Roucher, I. Plotton, C. Goursaud, V. Tardy et al., Evolution of steroids during pregnancy: Maternal, placental and fetal synthesis, Annales d'Endocrinologie, vol.77, pp.82-89, 2016.

A. Morisset, M. Dubé, R. Drolet, M. Pelletier, F. Labrie et al., Androgens in the maternal and fetal circulation: association with insulin resistance, J. Matern. Fetal. Neonatal. Med, vol.26, pp.513-519, 2013.

A. Mosbah and Y. Nabiel, Helicobacter pylori, Chlamydiae pneumoniae and trachomatis as probable etiological agents of preeclampsia, J. Matern. Fetal. Neonatal. Med, vol.29, pp.1607-1612, 2016.

P. *moussatche and T. J. Lyons, Non-genomic progesterone signalling and its noncanonical receptor, Biochemical Society Transactions, vol.40, pp.200-204, 2012.

V. Moutsatsou and R. E. Oakey, Oestriol binding to plasma proteins, J. Steroid Biochem, vol.29, pp.319-323, 1988.

J. W. Mueller, L. C. Gilligan, J. Idkowiak, W. Arlt, and P. A. Foster, The Regulation of Steroid Action by Sulfation and Desulfation, Endocr. Rev, vol.36, pp.526-563, 2015.

M. D. Mueller, J. L. Vigne, E. A. Pritts, V. Chao, E. Dreher et al., , 2003.

, Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells, Fertil. Steril, vol.79, pp.386-392

R. S. Muraoka-cook, H. Kurokawa, Y. Koh, J. T. Forbes, L. R. Roebuck et al., Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors, Cancer Res, vol.64, pp.9002-9011, 2004.

T. Nagamatsu, T. Fujii, M. Kusumi, L. Zou, T. Yamashita et al., Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia, Endocrinology, vol.145, pp.4838-4845, 2004.

D. R. Nelson, L. Koymans, T. Kamataki, J. J. Stegeman, R. Feyereisen et al., P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature, Pharmacogenetics, vol.6, pp.1-42, 1996.

O. Nevo, D. K. Lee, and I. Caniggia, Attenuation of VEGFR-2 expression by sFlt-1 and low oxygen in human placenta, PLoS ONE, vol.8, 2013.

T. D. Nguyen, L. Dolomie-fagour, A. Georges, and J. Corcuff, , 2008.

, Ann. Biol. Clin, vol.66, pp.493-497

Y. Nomura, R. M. John, A. B. Janssen, C. Davey, J. Finik et al., Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes, Archives of Gynecology and Obstetrics, 2017.

W. Norris, T. Nevers, S. Sharma, and S. Kalkunte, Review: hCG, preeclampsia and regulatory T cells, Placenta, vol.32, pp.182-185, 2011.

E. R. Norwitz, H. M. Stern, H. Grier, and A. Lee-parritz, Placenta percreta and uterine rupture associated with prior whole body radiation therapy, Obstet Gynecol, vol.98, pp.929-931, 2001.

A. D. Notation and G. E. Tagatz, Unconjugated estriol and 15alpha-hydroxyestriol in complicated pregnancies, Am. J. Obstet. Gynecol, vol.128, pp.747-756, 1977.

S. Ogawa, S. Inoue, T. Watanabe, H. Hiroi, A. Orimo et al., The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro, Biochem. Biophys. Res. Commun, vol.243, pp.122-126, 1998.

T. F. Ogle and B. K. Beyer, Steroid-binding specificity of the progesterone receptor from rat placenta, J. Steroid Biochem, vol.16, pp.147-150, 1982.

A. Ohkuchi, O. Ishibashi, C. Hirashima, K. Takahashi, S. Matsubara et al., Plasma level of hydroxysteroid (17-?) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio, Hypertens. Res, vol.35, pp.1152-1158, 2012.

R. N. Olsen, D. Woelkers, R. Dunsmoor-su, and D. Y. Lacoursiere, Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia, American Journal of Obstetrics and Gynecology, vol.207, pp.1-228, 2012.

,. *olsson, A. Dimberg, J. Kreuger, C. , and L. , VEGF receptor signalling -in control of vascular function, Nat. Rev. Mol. Cell Biol, vol.7, pp.359-371, 2006.

S. Opdahl, P. R. Romundstad, M. D. Alsaker, and L. J. Vatten, Hypertensive diseases in pregnancy and breast cancer risk, Br. J. Cancer, vol.107, pp.176-182, 2012.

J. M. Orshal and R. A. Khalil, Gender, sex hormones, and vascular tone, Am. J. Physiol. Regul. Integr. Comp. Physiol, vol.286, pp.233-249, 2004.

M. Palm, S. Basu, A. Larsson, L. Wernroth, H. Åkerud et al., A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy, Acta Obstet Gynecol Scand, vol.90, pp.1244-1251, 2011.

A. E. Palmer, W. T. London, D. L. Sly, and J. M. Rice, Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas), Lab. Anim. Sci, vol.29, pp.102-106, 1979.

P. Pan, H. Fu, L. Zhang, H. Huang, F. Luo et al., , 2010.

, Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells, BMC Cell Biol, vol.11, p.36

Y. Pang, J. Dong, T. , and P. , Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-?, Am. J. Physiol. Endocrinol. Metab, vol.308, pp.899-911, 2015.

J. E. Park, H. H. Chen, J. Winer, K. A. Houck, and N. Ferrara, Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR, J. Biol. Chem, vol.269, pp.25646-25654, 1994.

J. R. Pasqualini, C. , and G. , The anti-aromatase effect of progesterone and of its natural metabolites 20alpha-and 5alpha-dihydroprogesterone in the MCF-7aro breast cancer cell line, Anticancer Res, vol.28, pp.2129-2133, 2008.

H. Pavenstädt, W. Kriz, and M. Kretzler, Cell biology of the glomerular podocyte, Physiol. Rev, vol.83, pp.253-307, 2003.

U. Pecks, W. Rath, N. Kleine-eggebrecht, N. Maass, F. Voigt et al., Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies, Geburtshilfe Frauenheilkd, vol.76, pp.799-808, 2016.

D. Peleg, C. M. Kennedy, and S. K. Hunter, Intrauterine growth restriction: identification and management, Am Fam Physician, vol.58, pp.466-467, 1998.

M. E. Penning, K. W. Bloemenkamp, T. Van-der-zon, M. Zandbergen, J. M. Schutte et al., Association of Preeclampsia with Podocyte Turnover, Clinical Journal of the American Society of Nephrology, vol.9, pp.1377-1385, 2014.

*. Perez-sepulveda, A. España-perrot, P. P. Norwitz, E. R. Illanes, and S. E. , , 2013.

, Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia, Reprod Sci, vol.20, pp.1020-1029

M. Perrot-applanat, M. Deng, H. Fernandez, C. Lelaidier, G. Meduri et al.,

, Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels, J. Clin. Endocrinol. Metab, vol.78, pp.216-224

L. O. Perucci, K. B. Gomes, L. G. Freitas, L. C. Godoi, P. N. Alpoim et al., Soluble Endoglin, Transforming Growth Factor-Beta 1 and Soluble Tumor Necrosis Factor Alpha Receptors in Different Clinical Manifestations of Preeclampsia, PLoS ONE, vol.9, p.97632, 2014.

G. Petsas, U. Jeschke, D. U. Richter, V. Minas, A. Hammer et al., Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis, Mol. Hum. Reprod, vol.18, pp.535-545, 2012.

R. Pijnenborg, J. M. Bland, W. B. Robertson, and I. Brosens, Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy, Placenta, vol.4, pp.397-413, 1983.

R. Pijnenborg, L. Vercruysse, and M. Hanssens, The Uterine Spiral Arteries In Human Pregnancy: Facts and Controversies, Placenta, vol.27, pp.939-958, 2006.

R. Pion, R. Jaffe, G. Eriksson, N. Wiqvist, and E. Diczfalusy, Studies on the metabolism of C-21steroids in the human foeto-placental unit. I. Formation of a betaunsaturated 3-ketones in midterm placentas perfused in situ with pregnenolone and 17-alphahydroxypregnenolone, Acta Endocrinol, vol.48, pp.234-248, 1965.

E. Podjarny, G. Losonczy, and C. Baylis, Animal models of preeclampsia, Semin. Nephrol, vol.24, pp.596-606, 2004.

P. F. Policastro, S. Daniels-mcqueen, G. Carle, and I. Boime, A map of the hCG beta-LH beta gene cluster, J. Biol. Chem, vol.261, pp.5907-5916, 1986.

L. C. Poon and K. H. Nicolaides, Early Prediction of Preeclampsia, Obstetrics and Gynecology International, vol.2014, pp.1-11, 2014.

L. C. Poon, D. Wright, D. L. Rolnik, A. Syngelaki, J. L. Delgado et al., Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history, Am. J. Obstet. Gynecol, vol.217, pp.1-585, 2017.

P. Preziosi, E. Barrett-connor, L. Papoz, M. Roger, M. Saint-paul et al., Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the telecom study, The Journal of Clinical Endocrinology & Metabolism, vol.76, pp.283-287, 1993.

K. G. Pringle, K. L. Kind, A. N. Sferruzzi-perri, J. G. Thompson, and C. T. Roberts, Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy, Human Reproduction Update, vol.16, pp.415-431, 2010.

E. R. Prossnitz, L. A. Sklar, T. I. Oprea, and J. B. Arterburn, GPR30: a novel therapeutic target in estrogen-related disease, Trends Pharmacol. Sci, vol.29, pp.116-123, 2008.

S. Raam, G. S. Richardson, F. Bradley, D. Maclaughlin, L. Sun et al., Translocation of cytoplasmic estrogen receptors to the nucleus: immunohistochemical demonstration utilizing rabbit antibodies to estrogen receptors of mammary carcinomas, Breast Cancer Res. Treat, vol.3, pp.179-199, 1983.

S. A. Rahman, V. Hingorani, and K. R. Laumas, Biosynthesis of oestrogens and their inter-conversion in human placentae from normal and toxaemic pregnancies, Clin. Endocrinol. (Oxf), vol.4, pp.333-341, 1975.

S. Rana, A. S. Cerdeira, J. Wenger, S. Salahuddin, K. Lim et al., Plasma concentrations of soluble endoglin versus standard evaluation in patients with suspected preeclampsia, PLoS ONE, vol.7, p.48259, 2012.

J. K. Ranta, K. Raatikainen, J. Romppanen, K. Pulkki, and S. Heinonen, Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption, European Journal of Obstetrics & Gynecology and Reproductive Biology, vol.157, pp.48-52, 2011.

C. W. *redman, Pre-eclampsia: Definitions, paternal contributions and a four stage model, Pregnancy Hypertens, vol.1, pp.2-5, 2011.

C. W. *redman, Hypertension in pregnancy: the NICE guidelines, Heart, vol.97, pp.1967-1969, 2011.

C. W. *redman and I. L. Sargent, Latest advances in understanding preeclampsia, Science, vol.308, pp.1592-1594, 2005.

C. W. *redman and I. L. Sargent, Placental stress and pre-eclampsia: a revised view, Placenta, vol.30, 2009.

M. J. Reed, R. W. Cheng, M. Simmonds, W. Richmond, J. et al., Dietary lipids: an additional regulator of plasma levels of sex hormone binding globulin, J. Clin. Endocrinol. Metab, vol.64, pp.1083-1085, 1987.

K. Reisinger, N. Baal, T. Mckinnon, K. Münstedt, and M. Zygmunt, The gonadotropins: tissue-specific angiogenic factors?, Mol. Cell. Endocrinol, vol.269, pp.65-80, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00531904

C. M. Revankar, D. F. Cimino, L. A. Sklar, J. B. Arterburn, and E. R. Prossnitz, A transmembrane intracellular estrogen receptor mediates rapid cell signaling, Science, vol.307, pp.1625-1630, 2005.

S. Roberge, K. Nicolaides, S. Demers, J. Hyett, N. Chaillet et al., The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis, Am. J. Obstet. Gynecol, vol.216, pp.110-120, 2017.

C. J. Robinson and S. E. Stringer, The splice variants of vascular endothelial growth factor (VEGF) and their receptors, J. Cell. Sci, vol.114, pp.853-865, 2001.

D. P. Robinson and S. L. Klein, Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis, Hormones and Behavior, vol.62, pp.263-271, 2012.

M. A. Rodger, J. Gris, J. I. De-vries, I. Martinelli, É. Rey et al., Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials, Lancet, vol.388, pp.2629-2641, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01900640

D. A. Roess, M. A. Jewell, C. J. Philpott, and B. G. Barisas, The rotational diffusion of LH receptors differs when receptors are occupied by hCG versus LH and is increased by cytochalasin D, Biochim. Biophys. Acta, vol.1357, pp.98-106, 1997.

D. L. Rolnik, D. Wright, L. C. Poon, N. O'gorman, A. Syngelaki et al., Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia, New England Journal of Medicine, vol.377, pp.613-622, 2017.

R. Romero, A. Conde-agudelo, E. Da-fonseca, J. M. O'brien, E. Cetingoz et al., Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data, Am. J. Obstet. Gynecol, vol.218, pp.161-180, 2018.

L. S. Rosen, H. I. Hurwitz, M. K. Wong, J. Goldman, D. S. Mendelson et al., A Phase I First-in-Human Study of TRC105 (Anti-Endoglin Antibody) in Patients with Advanced Cancer, Clinical Cancer Research, vol.18, pp.4820-4829, 2012.

U. Rosing and K. Carlström, Serum levels of unconjugated and total oestrogens and dehydroepiandrosterone, progesterone and urinary oestriol excretion in preeclampsia, Gynecol. Obstet. Invest, vol.18, pp.199-205, 1984.

W. Rosner, The functions of corticosteroid-binding globulin and sex hormonebinding globulin: recent advances, Endocr. Rev, vol.11, pp.80-91, 1990.

P. Round, S. Das, K. Wahala, P. F. Van, and G. Hammond, Characterization of sex hormone binding globulin ligands with potential to enhance sex steroid action, Endocrine Abstracts, vol.58, p.680, 2018.

C. M. Salafia, J. C. Pezzullo, J. López-zeno, S. Simmens, V. K. Minior et al., Placental pathologic features of preterm preeclampsia, American Journal of Obstetrics and Gynecology, vol.173, pp.1097-1105, 1995.

J. B. Salom, M. C. Burguete, F. J. Pérez-asensio, G. Torregrosa, A. et al., , 2001.

, Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition, J. Cereb. Blood Flow Metab, vol.21, pp.422-429

L. Salomon, J. Bernard, B. De-stavola, M. Kenward, and Y. Ville, , 2007.

, J Gynecol Obstet Biol Reprod, vol.36, pp.50-56

D. A. Savitz, V. A. Danilack, S. M. Engel, B. Elston, and H. S. Lipkind, Descriptive Epidemiology of Chronic Hypertension, Gestational Hypertension, and Preeclampsia, Maternal and Child Health Journal, vol.18, pp.829-838, 1995.

J. Schneider, M. M. Huh, H. L. Bradlow, and J. Fishman, Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells, J. Biol. Chem, vol.259, pp.4840-4845, 1984.

A. Schumacher, N. Brachwitz, S. Sohr, K. Engeland, S. Langwisch et al., Human Chorionic Gonadotropin Attracts Regulatory T Cells into the Fetal-Maternal Interface during Early Human Pregnancy, The Journal of Immunology, vol.182, pp.5488-5497, 2009.

J. M. Schutte, N. W. Schuitemaker, and J. Van-roosmalen, Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands, Steegers, E. a. P., and Dutch Maternal Mortality Committee, vol.115, pp.732-736, 2008.

N. Schütze, G. Vollmer, and R. Knuppen, Catecholestrogens are agonists of estrogen receptor dependent gene expression in MCF-7 cells, J. Steroid Biochem. Mol. Biol, vol.48, pp.453-461, 1994.

J. Schwers, G. Eriksson, and E. Diczfalusy, 15alpha-hydroxylation : a new pathway of estrogen metabolism in the human fetus and newborn, Biochim. Biophys. Acta, vol.100, pp.313-316, 1965.

E. W. Seely and J. Ecker, Chronic Hypertension in Pregnancy, Circulation, vol.129, pp.1254-1261, 2014.

D. R. Senger, D. T. Connolly, L. Van-de-water, J. Feder, and H. F. Dvorak, Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor, Cancer Res, vol.50, pp.1774-1778, 1990.

J. K. Sethi and G. S. Hotamisligil, The role of TNF alpha in adipocyte metabolism, Semin. Cell Dev. Biol, vol.10, pp.19-29, 1999.

F. Shalaby, J. Rossant, T. P. Yamaguchi, M. Gertsenstein, X. F. Wu et al., Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice, Nature, vol.376, pp.62-66, 1995.

Y. G. Shanker and A. J. Rao, Progesterone receptor expression in the human placenta, Mol. Hum. Reprod, vol.5, pp.481-486, 1999.

T. S. Sherman, K. L. Chambliss, L. L. Gibson, M. C. Pace, M. E. Mendelsohn et al., Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium, Am. J. Respir. Cell Mol. Biol, vol.26, pp.610-616, 2002.

M. Shibuya, Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti-and Pro-Angiogenic Therapies, Genes & Cancer, vol.2, pp.1097-1105, 2011.

M. Shimodaira, T. Nakayama, I. Sato, N. Sato, N. Izawa et al., Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy, Endocrine, vol.42, pp.700-707, 2012.

S. E. *shoelson, J. Lee, and A. B. Goldfine, Inflammation and insulin resistance, J. Clin. Invest, vol.116, pp.1793-1801, 2006.

V. H. Shore, T. H. Wang, C. L. Wang, R. J. Torry, M. R. Caudle et al., , 1997.

, Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast, Placenta, vol.18, pp.657-665

B. Sibai, G. Dekker, and M. Kupferminc, Pre-eclampsia, Lancet, vol.365, pp.785-799, 2005.

B. M. Sibai, B. Mercer, and C. Sarinoglu, Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis, Am. J. Obstet. Gynecol, vol.165, pp.1408-1412, 1991.

J. Sibiude, J. Guibourdenche, M. Dionne, C. Le-ray, O. Anselem et al., Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction, PLoS ONE, vol.7, p.50208, 2012.

D. P. Sieveking, P. Lim, R. W. Chow, L. L. Dunn, S. Bao et al., A sex-specific role for androgens in angiogenesis, The Journal of Experimental Medicine, vol.207, pp.345-352, 2010.

P. K. Siiteri, The continuing saga of dehydroepiandrosterone (DHEA), J. Clin. Endocrinol. Metab, vol.90, pp.3795-3796, 2005.

P. K. Siiteri and P. C. Macdonald, Placental estrogen biosynthesis during human pregnancy, J. Clin. Endocrinol. Metab, vol.26, pp.751-761, 1966.

R. Smith, S. Mesiano, E. C. Chan, S. Brown, and R. B. Jaffe, Corticotropinreleasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells, J. Clin. Endocrinol. Metab, vol.83, pp.2916-2920, 1998.

V. Snegovskikh, E. Hodgson, M. Wehrum, G. Luo, E. Funai et al., 400: Human chorionic gonadotrophin (hCG) is produced by both syncytiotrophoblast and cytotrophoblast cells: A paradigm shift, American Journal of Obstetrics and Gynecology, vol.197, p.120, 2007.

A. Sobrino, M. Mata, A. Laguna-fernandez, S. Novella, P. J. Oviedo et al., Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells, PLoS ONE, vol.4, p.8242, 2009.

Y. Solak, B. Afsar, N. D. Vaziri, G. Aslan, C. E. Yalcin et al., Hypertension as an autoimmune and inflammatory disease, Hypertension Research, p.229, 2016.

L. Soucy-giguère, A. Tétu, S. Gauthier, M. Morand, F. Chandad et al., Periodontal Disease and Adverse Pregnancy Outcomes: A Prospective Study in a Low-Risk Population, J Obstet Gynaecol Can, vol.38, pp.346-350, 2016.

C. Souders, S. Maynard, J. Yan, Y. Wang, N. Boatright et al., Circulating Levels of sFlt1 Splice Variants as Predictive Markers for the Development of Preeclampsia, International Journal of Molecular Sciences, vol.16, pp.12436-12453, 2015.

H. E. Soydinc, I. Kan, T. Dal, M. S. Evsen, M. E. Sak et al., Evaluation of the relationship between preeclampsia and seropositivity of infectious disease in maternal plasma, Clin Ter, vol.164, pp.199-202, 2013.

K. Spencer, C. K. Yu, G. Rembouskos, R. Bindra, and K. H. Nicolaides, First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes, Hypertens Pregnancy, vol.24, pp.303-311, 2005.

F. Z. Stanczyk, All progestins are not created equal, Steroids, vol.68, pp.879-890, 2003.

*. Staun-ram, E. Shalev, and E. , Human trophoblast function during the implantation process, Reprod. Biol. Endocrinol, vol.3, p.56, 2005.

H. Stepan, A. Unversucht, N. Wessel, and R. Faber, Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion, Hypertension, vol.49, pp.818-824, 2007.

H. *stepan, I. Herraiz, D. Schlembach, S. Verlohren, S. Brennecke et al., Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice, Ultrasound Obstet Gynecol, vol.45, pp.241-246, 2015.

H. Stepan, M. Hund, M. Gencay, B. Denk, C. Dinkel et al., A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome, Hypertension in Pregnancy, vol.35, pp.295-305, 2016.

I. E. Stillman and S. A. Karumanchi, The glomerular injury of preeclampsia, J. Am. Soc. Nephrol, vol.18, pp.2281-2284, 2007.

S. St-jacques, M. Forte, S. J. Lye, and M. Letarte, Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy, Biol. Reprod, vol.51, pp.405-413, 1994.

F. Stormshak and C. V. Bishop, Board-invited review: Estrogen and progesterone signaling: genomic and nongenomic actions in domestic ruminants, J. Anim. Sci, vol.86, pp.299-315, 2008.

J. F. Strauss, L. K. Christenson, L. Devoto, and F. Martinez, Providing progesterone for pregnancy: control of cholesterol flux to the side-chain cleavage system, J. Reprod. Fertil. Suppl, vol.55, pp.3-12, 2000.

H. Strevens, D. Wide-swensson, A. Hansen, T. Horn, I. Ingemarsson et al., Glomerular endotheliosis in normal pregnancy and pre-eclampsia, BJOG, vol.110, pp.831-836, 2003.

D. Subtil, P. Goeusse, F. Puech, P. Lequien, S. Biausque et al., Aspirin (100 mg) used for prevention of preeclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study, BJOG, vol.110, pp.475-484, 2003.

A. Suhag and V. Berghella, Intrauterine Growth Restriction (IUGR): Etiology and Diagnosis, Current Obstetrics and Gynecology Reports, vol.2, pp.102-111, 2013.

M. Sullivan, M. Elder, and M. Swiet, Too little, too late, Am. J. Obstet. Gynecol, vol.181, pp.508-509, 1999.

Y. Sun, W. Niu, F. Du, C. Du, S. Li et al.,

, Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors, Journal of Hematology & Oncology, vol.9

*. Sutter-dub and M. T. , Rapid non-genomic and genomic responses to progestogens, estrogens, and glucocorticoids in the endocrine pancreatic B cell, the adipocyte and other cell types, Steroids, vol.67, pp.77-93, 2002.

R. Tamimi, P. Lagiou, L. J. Vatten, L. Mucci, D. Trichopoulos et al., Pregnancy hormones, pre-eclampsia, and implications for breast cancer risk in the offspring, Cancer Epidemiol. Biomarkers Prev, vol.12, pp.647-650, 2003.

D. Tannetta and I. Sargent, Placental Disease and the Maternal Syndrome of Preeclampsia: Missing Links?, Current Hypertension Reports, vol.15, pp.590-599, 2013.

D. S. Tannetta, R. A. Dragovic, C. Gardiner, C. W. Redman, and I. L. Sargent, Characterisation of syncytiotrophoblast vesicles in normal pregnancy and pre-eclampsia: expression of Flt-1 and endoglin, PLoS ONE, vol.8, p.56754, 2013.

A. H. Taylor, P. C. Mcparland, D. J. Taylor, and S. C. Bell, The cytoplasmic 60 kDa progesterone receptor isoform predominates in the human amniochorion and placenta at term, Reproductive Biology and Endocrinology, vol.7, p.231, 2009.

R. Thadhani, T. Kisner, H. Hagmann, V. Bossung, S. Noack et al., Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia, Circulation, vol.124, pp.940-950, 2011.

R. Thadhani, H. Hagmann, W. Schaarschmidt, B. Roth, T. Cingoez et al., Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia, 903-913. the international STRIDER Consortium, vol.27, 2016.

, Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): an international consortium of randomised placebo-controlled trials, BMC Pregnancy and Childbirth, vol.17

P. Thomas, Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone membrane receptor component 1 (PGMRC1) and their roles in mediating rapid progestin actions, Front Neuroendocrinol, vol.29, pp.292-312, 2008.

J. Thompson and G. Haven, Evaluation of a radioimmunoassay for serum unconjugated estriol using commercial reagents, Am. J. Clin. Pathol, vol.68, pp.474-480, 1977.

K. Toda, E. R. Simpson, C. R. Mendelson, Y. Shizuta, and M. W. Kilgore, Expression of the gene encoding aromatase cytochrome P450 (CYP19) in fetal tissues, Mol. Endocrinol, vol.8, pp.210-217, 1994.

M. H. Tong, H. Jiang, P. Liu, J. A. Lawson, L. F. Brass et al., Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferasedeficient mice, Nat. Med, vol.11, pp.153-159, 2005.

M. Toporsian, R. Gros, M. G. Kabir, S. Vera, K. Govindaraju et al., A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia, Circ. Res, vol.96, pp.684-692, 2005.

E. Torsney, R. Charlton, D. Parums, M. Collis, A. et al., Inducible expression of human endoglin during inflammation and wound healing in vivo, Inflamm. Res, vol.51, pp.464-470, 2002.

P. Toth, X. Li, C. V. Rao, S. R. Lincoln, J. S. Sanfilippo et al., Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries, J. Clin. Endocrinol. Metab, vol.79, pp.307-315, 1994.

A. L. Tranquilli, G. Dekker, L. Magee, J. Roberts, B. M. Sibai et al., The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP, Pregnancy Hypertens, vol.4, pp.97-104, 2014.

A. Trapani, L. F. Gonçalves, T. F. Trapani, S. Vieira, M. Pires et al., Perinatal and Hemodynamic Evaluation of Sildenafil Citrate for Preeclampsia Treatment: A Randomized Controlled Trial, Obstet Gynecol, vol.128, pp.253-259, 2016.

L. I. Trogstad, A. Eskild, A. L. Bruu, S. Jeansson, and P. A. Jenum, Is preeclampsia an infectious disease?, Acta Obstet Gynecol Scand, vol.80, pp.1036-1038, 2001.

M. Tsampalas, V. Gridelet, S. Berndt, J. Foidart, V. Geenen et al., Human chorionic gonadotropin: a hormone with immunological and angiogenic properties, J. Reprod. Immunol, vol.85, pp.93-98, 2010.

V. Tsatsaris, F. Goffin, and J. M. Foidart, Circulating angiogenic factors and preeclampsia, N. Engl. J. Med, vol.350, 2003.

C. Tse, G. Lefevre, N. Berkane, A. Flahault, K. Toumi et al., Increased serum maternal levels of the HER2 oncoprotein p105 ectodomain in preeclampsia, Clin. Chem. Lab. Med, vol.42, pp.142-146, 2004.

E. Tskitishvili, M. Nisolle, C. Munaut, C. Pequeux, C. Gerard et al., Estetrol attenuates neonatal hypoxic-ischemic brain injury, Experimental Neurology, vol.261, pp.298-307, 2014.

R. C. Tuckey, Progesterone synthesis by the human placenta, Placenta, vol.26, pp.273-281, 2005.

A. Turgut, A. Ozler, N. Y. Goruk, S. Y. Tunç, M. E. Sak et al., Serum levels of the adipokines, free fatty acids, and oxidative stress markers in obese and non-obese preeclamptic patients, Clin Exp Obstet Gynecol, vol.42, pp.473-479, 2015.

I. Ulmanen, J. Peränen, J. Tenhunen, C. Tilgmann, T. Karhunen et al., Expression and intracellular localization of catechol O-methyltransferase in transfected mammalian cells, Eur. J. Biochem, vol.243, pp.452-459, 1997.

S. Uzan, M. Beaufils, G. Breart, B. Bazin, C. Capitant et al., Prevention of fetal growth retardation with low-dose aspirin: findings of the EPREDA trial, Lancet, vol.337, pp.1427-1431, 1991.

H. Valensise, B. Vasapollo, G. Gagliardi, and G. P. Novelli, Early and Late Preeclampsia: Two Different Maternal Hemodynamic States in the Latent Phase of the Disease, Hypertension, vol.52, pp.873-880, 2008.

S. Venkatesha, M. Toporsian, C. Lam, J. Hanai, T. Mammoto et al., Soluble endoglin contributes to the pathogenesis of preeclampsia, Nat. Med, vol.12, pp.642-649, 2006.

S. Verlohren, I. Herraiz, O. Lapaire, D. Schlembach, H. Zeisler et al., New gestational phase-specific 233 test for preeclampsia, Hypertension, vol.63, pp.346-352, 2014.

M. Viglierchio, M. G. García, O. Riesco, D. M. Williamson, S. I. Williams et al., Progesterone receptors and progesterone concentration in serum and porcine maternal placental extracts, Placenta, vol.36, p.499, 2015.

M. Visser, C. F. Holinka, C. Bennink, and H. J. , First human exposure to exogenous single-dose oral estetrol in early postmenopausal women, Climacteric, vol.11, issue.1, pp.31-40, 2008.

A. E. Wallace, R. Fraser, and J. E. Cartwright, Extravillous trophoblast and decidual natural killer cells: a remodelling partnership, Hum. Reprod. Update, vol.18, pp.458-471, 2012.

S. W. Walsh, Progesterone and estradiol production by normal and preeclamptic placentas, Obstet Gynecol, vol.71, pp.222-226, 1988.

L. M. Walter, P. A. Rogers, and J. E. Girling, The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice, Reproduction, vol.129, pp.765-777, 2005.

Y. Wang, Q. Chen, M. Zhao, K. Walton, C. Harrison et al., Multiple Soluble TGF-? Receptors in Addition to Soluble Endoglin Are Elevated in Preeclamptic Serum and They Synergistically Inhibit TGF-? Signaling, The Journal of Clinical Endocrinology & Metabolism, vol.102, pp.3065-3074, 2017.

L. L. Wei, P. Hawkins, C. Baker, B. Norris, P. L. Sheridan et al., An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity, Mol. Endocrinol, vol.10, pp.1379-1387, 1996.

L. Weinstein, Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy, Am. J. Obstet. Gynecol, vol.142, pp.159-167, 1982.

K. C. Westerlind, K. J. Gibson, G. L. Evans, and R. T. Turner, The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions, J. Endocrinol, vol.167, pp.281-287, 2000.

U. Westphal, Steroid-protein interactions II, Monogr Endocrinol, vol.27, pp.1-603, 1986.

T. Wheeler, C. L. Elcock, A. , and F. W. , Angiogenesis and the placental environment, Placenta, vol.16, pp.289-296, 1995.

G. S. Whitley and J. E. Cartwright, Trophoblast-mediated spiral artery remodelling: a role for apoptosis, J. Anat, vol.215, pp.21-26, 2009.

J. P. Wiebe, Progesterone metabolites in breast cancer, Endocr. Relat. Cancer, vol.13, pp.717-738, 2006.

J. P. Wiebe, D. Muzia, J. Hu, D. Szwajcer, S. A. Hill et al., The 4-pregnene and 5alpha-pregnane progesterone metabolites formed in nontumorous and tumorous breast tissue have opposite effects on breast cell proliferation and adhesion, Cancer Res, vol.60, pp.936-943, 2000.

J. P. Wiebe, G. Zhang, I. Welch, and H. T. Cadieux-pitre, Progesterone metabolites regulate induction, growth, and suppression of estrogen-and progesterone receptor-negative human breast cell tumors, Breast Cancer Research, vol.15, 2013.

D. Williams, Long-Term Complications of Preeclampsia, Seminars in Nephrology, vol.31, pp.111-122, 2011.

H. E. Witkowska, M. Carlquist, O. Engström, B. Carlsson, T. Bonn et al., Characterization of bacterially expressed rat estrogen receptor beta ligand binding domain by mass spectrometry: structural comparison with estrogen receptor alpha, Steroids, vol.62, pp.621-631, 1997.

A. G. Witlin and B. M. Sibai, Perinatal and maternal outcome following abruptio placentae, Hypertens Pregnancy, vol.20, pp.195-203, 2001.

H. A. *wollmann, Intrauterine growth restriction: definition and etiology, Horm. Res, 1998.

J. Woolard, W. Wang, H. S. Bevan, Y. Qiu, L. Morbidelli et al., VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, Cancer Res, vol.64, pp.7822-7835, 2004.

C. Worda, M. O. Sator, C. Schneeberger, T. Jantschev, K. Ferlitsch et al., Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women, Hum. Reprod, vol.18, pp.262-266, 2003.

, Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy, Am. J. Obstet. Gynecol, vol.183, pp.1-22, 2000.

L. Wu, M. Einstein, W. M. Geissler, H. K. Chan, K. O. Elliston et al., Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity, J. Biol. Chem, vol.268, pp.12964-12969, 1993.

S. Wu, C. Kim, L. Baer, and X. Zhu, Bevacizumab Increases Risk for Severe Proteinuria in Cancer Patients, Journal of the American Society of Nephrology, vol.21, pp.1381-1389, 2010.

F. Xie, Y. Hu, L. A. Magee, D. M. Money, D. M. Patrick et al., An association between cytomegalovirus infection and pre-eclampsia: a case-control study and data synthesis, Acta Obstet Gynecol Scand, vol.89, pp.1162-1167, 2010.

J. D. Yager and N. E. Davidson, Estrogen carcinogenesis in breast cancer, N. Engl. J. Med, vol.354, pp.270-282, 2006.

H. Yamashita, H. Ichijo, S. Grimsby, A. Morén, P. Ten-dijke et al., , 1994.

, Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta, J. Biol. Chem, vol.269, 1995.

C. Yeh, K. Chao, and S. J. Huang, Innate Immunity, Decidual Cells, and Preeclampsia, Reproductive Sciences, vol.20, pp.339-353, 2013.

H. Yonekura, S. Sakurai, X. Liu, H. Migita, H. Wang et al., Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis, J. Biol. Chem, vol.274, pp.35172-35178, 1999.

N. Yoshida and Y. Osawa, Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization, Biochemistry, vol.30, pp.3003-3010, 1991.

S. Young and B. Lessey, Progesterone Function in Human Endometrium: Clinical Perspectives, Seminars in Reproductive Medicine, vol.28, pp.5-016, 2010.

E. V. Younglai, Y. J. Wu, T. K. Kwan, and C. Kwan, Non-genomic action of estradiol and progesterone on cytosolic calcium concentrations in primary cultures of human granulosa-lutein cells, Hum. Reprod, vol.20, pp.2383-2390, 2005.

C. Yu, A. Papageorghiou, R. Bindra, K. Spencer, and K. Nicolaides, Secondtrimester sex hormone-binding globulin and subsequent development of pre-eclampsia, The Journal of Maternal-Fetal & Neonatal Medicine, vol.16, pp.158-162, 2004.

E. Zachariades, D. Mparmpakas, Y. Pang, M. Rand-weaver, P. Thomas et al., Changes in placental progesterone receptors in term and preterm labour, Placenta, vol.33, pp.367-372, 2012.

H. Zeisler, M. O. Sator, and E. A. Joura, Serum levels of progesterone in patients with preeclampsia, Wien. Klin. Wochenschr, vol.112, pp.362-364, 2000.

H. Zeisler, E. Llurba, F. Chantraine, M. Vatish, A. C. Staff et al., Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia, N. Engl. J. Med, vol.374, pp.13-22, 2016.

J. Zhang and W. Zhang, , 2012.

, Zhonghua Yi Xue Za Zhi, vol.92, pp.1413-1415

S. Zhao, Y. Gu, R. Fan, L. J. Groome, D. Cooper et al., Proteases and sFlt-1 Release in the Human Placenta, Placenta, vol.31, pp.512-518, 2010.

X. Zhu, S. Wu, W. L. Dahut, and C. R. Parikh, Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis, Am. J. Kidney Dis, vol.49, pp.186-193, 2007.