Successful generation of haploid gametes from diploid germ cells through meiotic division is a critical, if not the most important, step for successful sexual reproduction. Despite the importance of meiosis, molecular mechanisms governing its control remain poorly understood. The initiation of meiosis in germ cells depends on their exposure to extrinsic retinoic acid (RA); however, the sufficiency (or even the requirement) for RA in meiosis has been an on-going debate, and other factors from the gonadal somatic environment is likely to be involved.
Inspired by previous studies in primordial germ cell-like cells (PGCLCs) (1,2) that demonstrated the role of BMP signalling in female fate specification in vitro, we investigated the requirement for BMP signalling in mouse fetal germ cells using a transgenic mouse model that allows temporally controlled depletion of BMPR1A-mediated BMP signalling specifically in the germ cells (Bmpr1aΔPGC). We verified, for the first time in vivo, that BMP signalling promotes meiotic progression in fetal ovarian germ cells. Initiation of Stra8 expression was found to be independent upon BMP signalling, although aberrant cytoplasmic STRA8 was observed in Bmpr1a-deficient ovarian germ cells. Meiotic progression was delayed and mitotic exit was compromised in Bmpr1a-deficient germ cells. Differential gene expression among Bmpr1aΔPGC, Stra8null, and their control ovaries showed that in mouse fetal ovaries, BMP signalling and STRA8 are both responsible (directly or indirectly) for the downregulation of pluripotency factors and early primordial germ cell-related genes, but BMP signalling is required also for suppressing mitotic cell cycle genes and male germ cell-specific genes, and to regulate the dosage of meiotic progression genes. We conclude that in mouse fetal germ cells, BMP signalling and RA-induced STRA8 together ensure the loss of pluripotency, proper exit of mitotic cell cycle and entry of meiotic cycle, and the subsequent progression through meiosis.