Reproduction Abstracts

Context: In mammalian female germ cells, meiotic entry occurs during fetal life. The current model places retinoic acid (RA) as a key signal inducing meiotic initiation by activating the expression of stimulated by retinoic acid 8 (Stra8), a necessary factor for pre-meiotic chromosomal replication. However, the requirement of RA for meiotic initiation has been recently questioned in the female germ cells.

Material and method: To clarify whether RA receptors regulate Stra8 expression in murine fetal ovaries, we performed treatments with RAR-antagonists in organotypic cultures and analyzed the expression of RA target genes and meiotic genes. We performed a fine study of meiotic genes expression around the time of meiosis initiation in fetal gonads. Meiosis inducer candidate genes were studied using siRNA and plasmids in a cell line.

Results and discussion: Treatments with RAR-antagonists evidenced that Stra8 expression may not be directly driven by endogenous RA in the fetal ovary. The precise study of meiotic gene expression revealed that meiotic genes are expressed in three distinct waves and that some are expressed prior to Stra8. Interestingly, we observed that other genes previously identified in transcriptome analyses as specific of female germ cells were expressed before Stra8. These may be considered as new meiosis inducing factors and their role was investigated using F9 cells that express many meiotic genes. Altogether our work challenges the place of Stra8 as the only gatekeeper of the induction of the meiotic program. In conclusion, the gene network regulating female meiotic entry appears more complex than expected.