Reproduction Abstracts

Mammalian gonads arise in both sexes from bilateral urogenital ridges that have the potential to develop as ovaries or testes. In mice, the genital ridges are first evident at embryonic day (E) 9.5. At E10.5, a critical switch in gonad development occurs in which XY gonads express the testis-determining gene (sex-determining region Y chromosome) Sry. Sry belongs to the SOX family of nuclear transcription factors. Male sex determination is governed by Sry-dependent activation of another SOX protein, namely, Sox9, leading to differentiation of Sertoli cells and other testicular cell lineages, and to testis development. In contrast, the absence of Sry expression in XX bipotential gonads leads to ovary development. We have recently discovered that another SOX family member, Sox4, is strongly and specifically expressed in the testis cords of XY embryos at E11.5, the earliest stage of testis development. Remarkably, our preliminary data indicates that XY Sox4-deficient embryos develop ovaries or ambiguous ‘ovostestis’. At E14.5, when the testis should be rounding in shape and migrating caudally towards the bladder, XY Sox4-deficient embryos exhibit an elongated gonad morphologically indistinguishable from an ovary (n=4), which remains rostrally located and axiolateral to the kidneys, similar to what is observed in normal XX embryos. Given the established role of other members of the Sox family in controlling male differentiation, our exciting preliminary findings strongly support a role for Sox4 in XY testis development in vivo.