The Battle of the Sexes: Opposing Pathways in Sex Determination

In mammals, a primordial gonad forms in XY and XX embryos that develops into a testis or an ovary depending on expression of Sry. Sry induces cell signalling pathways, including proliferation of Sertoli precursors and migration of peritubular myoid and vascular cells from the mesonephros. These events result in increased testis size and testis cord organization. Testis cord formation normally prohibits germ cells from entering meiosis. Ovarian fate is initiated in the absence of Sry, and has been proposed to be dependent upon the presence of meiotic germ cells in the gonad. We have shown that a developmental window exists during which testis development can be experimentally induced in XX gonads. This window closes just prior to the time that germ cells enter meiosis. Based on our work and much work that has preceded it, we suggest that the autonomous entry of germ cells into meiosis initiates the ovarian pathway and blocks testis development. Sry opposes this pathway by initiating testis cord formation prior to meiosis which sequesters germ cells inside cords and arrests them in mitosis. Current experiments in the lab address the hypothesis that cord formation and germ cell entry into meiosis are competing pathways in gonad development.