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Modèle murin invalidé pour les LXRs : dyslipidémie et impact sur la maturation post-testiculaire des gamètes

Abstract : The acquisition of fertile spermatozoa is a long and multi-stage process, beginning with the production of male gametes in the testis. Spermatozoa then undergo two successive maturation steps, first during the epididymal transit and then in the female genital tract during the capacitation process. The post-testicular maturation particularly impacts sperm lipid composition, leading to a higher membrane fluidity considered to be essential for fertilization.The results presented in this work show the importance of epididymal lipid homeostasis for sperm lipid maturation and acquisition of fertilizing ability. At the molecular level, lipid homeostasis is regulated by the LXRs (α and β isoforms), the oxysterol nuclear receptors (NR1H3 and NR1H2, respectively). A cholesterol-enriched diet in young LXR-null mice leads to infertility with a specific epididymal alteration. Sperm epididymal maturation is altered, leading to defects in lipid and protein composition of the spermatic plasma membrane. These defects have detrimental effects on the capacitation process, characterized by disturbances of calcium flows and tyrosine phosphorylation.In addition to their endocrine effects, dyslipidemia also appear to affect post-testicular maturation. These results have to be considered in the context of ART protocols, since the plasma lipid status is not part of the routine examinations for couples in ART protocols. Concomitantly, in France, 55% of men aged 30-54 are dyslipidemic, suggesting that these lipid metabolic disorders could alter sperm post-testicular maturation, causing a number of infertility and / or ART failures.
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Submitted on : Wednesday, May 16, 2018 - 2:09:07 PM
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Marjorie Whitfield. Modèle murin invalidé pour les LXRs : dyslipidémie et impact sur la maturation post-testiculaire des gamètes. Reproduction sexuée. Université Clermont Auvergne, 2017. Français. ⟨NNT : 2017CLFAC010⟩. ⟨tel-01793278⟩

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