Implication de "Liver X Receptors" dans la physiopathologie des gonades

Abstract : Sterility affects 15 % of French population and its prevalence is propagating since four or five decades. Many human physiological and epidemiological arguments support the impact of lipid homeostasis on the gonads; indeed, cholesterol is a key regulator of steroidogenesis and gametogenesis. Nevertheless, the molecular mechanisms remain hidden. Liver X receptors alpha and beta (LXRα and β) belong to the superfamily of nuclear receptors and are activated upon binding to oxysterols. LXRs are mainly implicated in cholesterol homeostasis. Increasing bulk of literature identified these non-steroid nuclear receptors as major regulators of the gonad physiology. This work uncovers previously unidentified putative roles of LXRs and ability of cholecterol excess to alter male and female germ cell maturation. Herein, we analyse a new mouse strain (Lxrαϐ-/-:AMHLxrϐ) re-expressing LXRβ under control of AMH promoter (specific to Sertoli in testis and granulosa cells in ovary) in a background of Lxrαϐ-/- mouse. Our results identify LXRs as primordial to maintain male and female fertility. They have pleotropic « non-classical » roles ranging from lipid homeostasis to the regulation of germ cell maturation and bi-directional control of steroid synthesis.If the cellular defects in the absence of LXRs within the testis are significant, they are generally compensated and consequently, single cell compartment is tolerated.Unlike the testis, LXRβ in the granulosa cells is « the regulator » of multiple mechanisms essential for follicle maturation, ovocyte survival and for controlled ovulation. LXRβ is therefore a potnetial target to regulate female fertility and to prevent ovarian hyperstimulation syndrome.Our results open the perspectives for the identification of new diagnostic and/or prognostic markers in both male and female fertility.
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Salwan Maqdasy. Implication de "Liver X Receptors" dans la physiopathologie des gonades. Sciences agricoles. Université Blaise Pascal - Clermont-Ferrand II, 2016. Français. ⟨NNT : 2016CLF22713⟩. ⟨tel-01967605⟩

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