Germ cells respond to molecular cues that regulate their sex-specific development in the fetal gonads. In ovaries, germ cells enter meiosis whereas in testes, germ cells arrest mitotically and do not enter meiosis until puberty. We recently showed that germ cells in the mouse fetal ovary are triggered to enter meiosis by the signalling molecule retinoic acid (RA), produced in the adjacent mesonephros. In the developing testis, germ cells are not exposed to RA due to the expression of the RA-degrading enzyme CYP26B1. In Cyp26b1-null mice, RA levels are elevated and XY germ cells in the developing testis enter meiosis.
Our recent studies point to an alternative source of RA within developing mouse gonads, and to a new role for RA in the somatic differentiation of the fetal gonads, promoting ovarian and antagonizing testis development. Our results suggest that disturbances in RA metabolism may underlie some cases of gonadal dysgenesis in humans.