Meiosis and retinoic acid in the mouse fetal gonads: An unforeseen twist.

Abstract

In mammals, differentiation of germ cells is crucial for sexual reproduction, involving complex signaling pathways and environmental cues defined by the somatic cells of the gonads. This review examines the long-standing model positing that all-trans retinoic acid (ATRA) acts as a meiosis-inducing substance (MIS) in the fetal ovary by inducing expression of STRA8 in female germ cells, while CYP26B1 serves as a meiosis-preventing substance (MPS) in the fetal testis by degrading ATRA and preventing STRA8 expression in the male germ cells until postnatal development. Recent genetic studies in the mouse challenge this paradigm, revealing that meiosis initiation in female germ cells can occur independently of ATRA signaling, with key roles played by other intrinsic factors like DAZL and DMRT1, and extrinsic signals such as BMPs and vitamin C. Thus, ATRA can no longer be considered as 'the' long-searched MIS. Furthermore, evidence indicates that CYP26B1 does not prevent meiosis by degrading ATRA in the fetal testis, but acts by degrading an unidentified MIS or synthesizing an equally unknown MPS. By emphasizing the necessity of genetic loss-of-function approaches to accurately delineate the roles of signaling molecules such ATRA in vivo, this chapter calls for a reevaluation of the mechanisms instructing and preventing meiosis initiation in the fetal ovary and testis, respectively. It highlights the need for further research into the molecular identities of the signals involved in these processes.