How Germ Cells Determine Their Own Sexual Fate in Mice

Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction mechanism has not received much attention until relatively recently. This is because the issue of sexual differentiation has generally been considered a theme of somatic cells to make a testis or ovary. Basically, the sex of individual somatic cells and germ cells matches. Therefore, the sex of germ cells is thought to follow the sex of somatic cells once determined. However, researchers realized that a big, open question remained: What somatic cell signals actually induce the sexual differentiation of germ cells and what is the sex determinant in germ cells?

In vitro experiments demonstrated that 2 somatic signals (BMP and RA) act directly on germ cells to induce oogonia. Therefore, these 2 signals may be referred to as oogonia inducers. From the viewpoint of germ cells, an independent experiment identified SMAD4 and STRA8, which are directly downstream of BMP and RA, respectively, acting in germ cells as female determinants. However, what about male? If these factors are female determinants, their absence may result in the induction of spermatogonia. This may be true in vivo because germ cells enter a male pathway if they do not receive these signals even in the ovary. However, this has not been confirmed in an in vitro culture system. There should be signals required for germ cells to enter a male pathway.

The important message is that although testis-specific factors secreted from the testis are considered to include male-inducing factors for germ cells, this may not be the case, and the male-inducing factor, if it exists, also exists in the ovary.