Abstract EN:

The molecular mechanisms governing the sexual determination and differentiation are poorly understood. These phenomena are controlled by a cascade of events, which involves many genes. All the interest of our work was to study the role of four molecules: Wnt4, POF1B, PACAP and VIP in male and female sexual determination and differentiation. We observed, in vivo, that the absence of VIP and PACAP is associated with a reduction of the testicular steroidogenesis and a preservation of the testicular structure in the aged animals. This protection against testicular aging is associated with a reduced peroxinitrite production and with a reduction of the number of testicular cells undergoing apoptosis. The studies on POF1B revealed that this molecule is capable, in vitro, to bind the non-muscle actin filaments. The presence of the R329Q variant reduces the capacity of binding of POF1B to these filaments of actin. We thus propose that POF1B, expressed early during development, is a factor involved in cell divisions governing the final stock of oocytes. The changes within this gene, and specifically the presence of the R329Q variant, could be responsible for premature ovarian failure. Our work undertaken on Wnt4 shows that in vitro, this molecule inhibits the canonical pathway, independently of GSK3β. Moreover, Wnt4 allows the stabilization of β catenin rather than its degradation, probably through the regulation of the Siah1 protein. Also, in vivo and in vitro, Wnt4 directs the β catenin to the cellular membrane and in vitro, Wnt4 increases cell-cell adhesion in a dose-dependent manner. We thus suppose that Wnt4, while directing the β catenin at the membrane, enhance cell-cell adhesions but inhibits the cellular migration.