The Role of m(6)A on Female Reproduction and Fertility: From Gonad Development to Ovarian Aging

The growth and maturation of oocyte is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. N6-methyladenosine (m(6)A) is the most prevalent epigenetic modification in mRNA, and precisely regulates the RNA metabolism as well as gene expression in diverse physiological processes. Recent studies showed that m(6)A modification and regulators were essential for the process of ovarian development and its aberrant manifestation could result in ovarian aging. Moreover, the specific deficiency of m(6)A regulators caused oocyte maturation disorder and female infertility with defective meiotic initiation, subsequently the oocyte failed to undergo germinal vesicle breakdown and consequently lost the ability to resume meiosis by disrupting spindle organization as well as chromosome alignment. Accumulating evidence showed that dysregulated m(6)A modification contributed to ovarian diseases including polycystic ovarian syndrome (PCOS), primary ovarian insufficiency (POI), ovarian aging and other ovarian function disorders. However, the complex and subtle mechanism of m(6)A modification involved in female reproduction and fertility is still unknown. In this review, we have summarized the current findings of the RNA m(6)A modification and its regulators in ovarian life cycle and female ovarian diseases. And we also discussed the role and potential clinical application of the RNA m(6)A modification in promoting oocyte maturation and delaying the reproduction aging.