Progesterone regulates chicken embryonic germ cell meiotic initiation independent of retinoic acid signaling

The signaling molecule retinoic acid (RA) is known to trigger germ cells to enter meiosis. However, RA may not be the only secreted inducer of meiosis. Our previous data indicate that luteinizing hormone also promotes germ cell meiotic initiation by upregulating 3βHSDII transcription. Here, using chicken embryos, we investigate the role of progesterone (P₄) in regulating germ cell meiotic initiation. Progesterone treatment at embryonic Day 9.5 accelerated germ cell meiosis entry in the female chicken embryos. However, P₄ treatment in vivo did no influence on testicular germ cells but triggered their meiotic initiation in the cultured testes. As treatment with an RA receptor (RAR) inhibitor did not block the stimulatory effect of P₄ on germ cell meiotic initiation, this P₄ stimulatory effect seems to be independent of RAR-mediated signaling. The abundance of RA metabolism-related enzymes and RAR (RARβ) mRNAs did not differ significantly between P₄-treated and control individuals. The RA concentration in the ovaries remained unchanged by P₄ treatment in vivo. Because no inhibition by the P₄ receptor (PR) nuclear receptor antagonist mifepristone on P₄ effect was observed in either in vitro or in vivo experiments, the effect of P₄ on germ cell meiotic initiation is probably mediated by membrane PRs (mPR). The mPRα, mPRβ, and mPRγ mRNAs were all expressed in the embryonic ovaries. The expression of mPRα and mPRβ was higher than that of mPRγ. Immunohistochemical results showed that mPRα-positive cells were mainly scattered in the ovarian cortex area where most germ cells were distributed. The mPRβ-positive cells were widely distributed in the ovaries, and positive cells were clustered with a similar morphology to that of germ cell clusters. In conclusion, P₄ may regulate embryonic germ cell meiotic initiation independent of RA signaling through the membrane PRs. This study provides a new insight into the mechanisms of germ cell meiotic initiation in the chicken.