Ovarian aging is a natural process characterized by a decline in both the quantity and quality of oocytes, which subsequently leads to diminished fertility, particularly in women over the age of 35. Given the societal trend toward postponing childbirth, it is imperative to understand the molecular mechanisms that underpin ovarian aging to address infertility issues. Melatonin (MT) is recognized for its therapeutic potential in mitigating ovarian aging; however, the specific epigenetic mechanisms involved, particularly concerning m 6A methylation, remain inadequately defined. Our investigation demonstrates that MT mitigates ovarian aging in murine models, significantly decreasing m 6A methylation levels. In vitro analyses of ovarian granulosa (KGN) cells reveals a marked increase in YTHDF2 expression, with differentially methylated genes being notably enriched in the polyubiquitination pathway. Further examination shows that YTHDF2 enhances the expression of the E3 ligase UBE3C by modulating the m 6A methylation of UBE3C mRNA, thereby reducing the expression of the P53 senescence factor and alleviating the effects of ovarian aging.
Keywords: UBE3C; YTHDF2; mA; melatonin; ovarian aging; ubiquitination.