Cyclic AMP In Oocytes Controls Meiotic Prophase I And Primordial Folliculogenesis In The Perinatal Mouse Ovary

Follicle is the functional unit of mammalian ovaries. Different form spermatogenesis, a fixed population of primordial follicles forms during the perinatal stage and the oocytes contained are arrested at the dictyate stage of meiotic prophase I. Once the primordial follicle pool establishes, oocytes could not renew themselves in postnatal or adult life. Therefore, the primordial follicle pool represents the entirety of female reproductive potential over the life span. Proper oogenesis and folliculogenesis in the perinatal ovary are essential for female fertility, however, the mechanisms regulating these processes remain unclear.Cyclic AMP (cAMP) is a well-characterized intracellular second messenger which plays a pivotal role in the arrest and resumption of meiosis in oocytes of adult ovaries. Although the function of cAMP in regulating late stages of meiosis in activated oocytes has been extensively studied, it is unclear whether cAMP contributes to early oocyte meiosis and what the mechanism of its involvement might be.In the current study, we showed that the early meiotic development of oocytes was closely correlated with increased levels of intra-oocyte cAMP. Based on mRNA expression studies, Adcy2was likely to be the dominant isoform in perinatal ovaries, and the staining pattern of ADCY2suggested that cAMP was likely to be predominantly produced by oocytes during early oogenesis.Inhibiting cAMP synthesis in fetal ovaries delayed oocyte meiotic progression and inhibited the disassembly and degradation of synaptonemal complex protein1(SYCP1). In addition, blocking the gap junction did not affect the meiotic progress of oocytes, indicated that the cAMP used for meiotic development was synthesised by oocytes.Furthermore, inhibiting cAMP synthesis in in vitro cultured fetal ovaries disrupted a series of genes that had been reported to regulate early oogenesis and folliculogenesis and led to failure of primordial follicle formation at last. Finally, using an in situ oocyte chromosome analysis approach, we found that the dictyate arrest of oocytes was essential for primordial follicle formation under physiological conditions.In conclusion, our results indicate that oocyte-derived cAMP is important for early oogenesis and folliculogenesis in mice. These findings could contribute to opening new avenues of research to expand our understanding of physiological and pathological processes in the mammalian ovary.