Les organes centraux du tractus urogenital sont le testicule et l’ovaire, qui assurent la product... more Les organes centraux du tractus urogenital sont le testicule et l’ovaire, qui assurent la production de gametes et d’hormones, et donc la fertilite de l’individu. Ces deux organes, parfaitement distincts et complementaires, ont pour origine une gonade bipotentielle qui s’engagera vers une trajectoire de differenciation masculine ou feminine au cours de la vie fœtale. Les deux gonades vont par la suite subir plusieurs phases de differenciation et de developpement de leurs populations cellulaires, afin d’acquerir leurs fonctions propres qui leur permettront d’assumer leur role a l’âge adulte. Depuis plus d’une quinzaine d’annees, le concept de syndrome de dysgenesie testiculaire fait etat d’un lien entre l’exposition du fœtus a des composes environnementaux et des anomalies du tractus urogenital. Bien que sujette a de vifs debats au sein de la communaute scientifique, cette hypothese a attire l’attention de la recherche sur les consequences de l’exposition des meres aux xenobiotiques ...
STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads a... more STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis and ovary development in humans? SUMMARY ANSWER The characterization of a dynamically regulated protein-coding and non-coding transcriptional landscape in developing human gonads of both sexes highlights a large number of potential key regulators that show an early sexually dimorphic expression pattern. WHAT IS KNOWN ALREADY Gonadal sex differentiation is orchestrated by a sexually dimorphic gene expression program in XX and XY developing fetal gonads. A comprehensive characterization of its non-coding counterpart offers promising perspectives for deciphering the molecular events underpinning gonad development and for a complete understanding of the etiology of disorders of sex development in humans. STUDY DESIGN, SIZE, DURATION To further investigate the protein-coding and non-coding transcriptional landscape during gonad differentiat...
Sex determination of the gonads begins with fate specification of gonadal supporting cells into e... more Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian granulosa cells or testicular Sertoli cells. This process of fate specification hinges on a balance of transcriptional control. We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, goat and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity, and combined loss of RUNX1 and FOXL2 results in masculinization of the fetal ovaries. At the chromatin level, RUNX1 occupancy overlaps partially with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 target a common set of genes. These findings identify RUNX1, with an ovary-biased pattern conserved across species, as a novel regulator in securing the identity of ovarian supporti...
Les organes centraux du tractus urogenital sont le testicule et l’ovaire, qui assurent la product... more Les organes centraux du tractus urogenital sont le testicule et l’ovaire, qui assurent la production de gametes et d’hormones, et donc la fertilite de l’individu. Ces deux organes, parfaitement distincts et complementaires, ont pour origine une gonade bipotentielle qui s’engagera vers une trajectoire de differenciation masculine ou feminine au cours de la vie fœtale. Les deux gonades vont par la suite subir plusieurs phases de differenciation et de developpement de leurs populations cellulaires, afin d’acquerir leurs fonctions propres qui leur permettront d’assumer leur role a l’âge adulte. Depuis plus d’une quinzaine d’annees, le concept de syndrome de dysgenesie testiculaire fait etat d’un lien entre l’exposition du fœtus a des composes environnementaux et des anomalies du tractus urogenital. Bien que sujette a de vifs debats au sein de la communaute scientifique, cette hypothese a attire l’attention de la recherche sur les consequences de l’exposition des meres aux xenobiotiques ...
STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads a... more STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis and ovary development in humans? SUMMARY ANSWER The characterization of a dynamically regulated protein-coding and non-coding transcriptional landscape in developing human gonads of both sexes highlights a large number of potential key regulators that show an early sexually dimorphic expression pattern. WHAT IS KNOWN ALREADY Gonadal sex differentiation is orchestrated by a sexually dimorphic gene expression program in XX and XY developing fetal gonads. A comprehensive characterization of its non-coding counterpart offers promising perspectives for deciphering the molecular events underpinning gonad development and for a complete understanding of the etiology of disorders of sex development in humans. STUDY DESIGN, SIZE, DURATION To further investigate the protein-coding and non-coding transcriptional landscape during gonad differentiat...
Sex determination of the gonads begins with fate specification of gonadal supporting cells into e... more Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian granulosa cells or testicular Sertoli cells. This process of fate specification hinges on a balance of transcriptional control. We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, goat and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity, and combined loss of RUNX1 and FOXL2 results in masculinization of the fetal ovaries. At the chromatin level, RUNX1 occupancy overlaps partially with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 target a common set of genes. These findings identify RUNX1, with an ovary-biased pattern conserved across species, as a novel regulator in securing the identity of ovarian supporti...
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