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Rôles de FOXL2 dans la physiologie endométriale chez les bovins

Abstract : Implantation is a critical milestone ensuring a successful pregnancy and normal post-natal development in mammals. Implantation is defined as the establishment of cellular and permanent interactions between a receptive endometrium and a competent and synchronised embryo. Endometrium has been proposed to be a biological sensor of embryo quality that drives the developmental trajectory of the conceptus until term. Previous data from our team and others have suggested major biological roles for FOXL2 – a key transcription factor for the establishment and maintenance of ovarian function- in the development and functions of the mammalian endometrium. The aim of my work was to provide new insights on the contribution of FOXL2 to the regulation of the endometrial function in dairy cattle. We first evaluated the consequences of variations in maternal metabolism on the endometrial expression of FOXL2 and a selection of candidate genes. Our data demonstrated that, in Holstein primiparous females dried immediately after parturition, FOXL2 expression was increased whereas antioxidant enzymes expression was decreased in the endometrium at implantation. Using an in vitro model of primary cultures of bovine endometrial cells (fibroblasts and glandular epithelial cells) transiently overexpressing FOXL2, expression of genes encoding antioxidant enzymes did not appear to be FOXL2 dependant. Based on our in vitro experimental model, gene expression profiles were then determined using a bovine custom oligoarray. Data analyses unveil differences in FOXL2-regulated genes according to endometrial cell origin. As in the ovary, FOXL2 regulated sets of genes related to "immune response", "apoptosis" and "sex determination". Our results also highlighted regulation of endometrium-specific genes by FOXL2 including “response to type I interferon” and “extracellular matrix modification”. Altogether our data support the involvement of FOXL2 in the regulation of bovine endometrial physiology that deserves to be analyzed in other mammalian species.
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Audrey Lesage. Rôles de FOXL2 dans la physiologie endométriale chez les bovins. Biologie de la reproduction. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS422⟩. ⟨tel-01865815v2⟩

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