Role of epigenetic regulation in diminished ovarian reserve.

Diminished ovarian reserve (DOR) is characterized by a decrease in the number and quality of oocytes, with its incidence increasing annually. Its pathogenesis remains unclear, making it one of the most challenging problems in the field of assisted reproduction. Epigenetic modification, a molecular mechanism affecting genomic activity and expression without altering the DNA sequence, has been widely studied in reproductive medicine and has attracted considerable attention regarding DOR. This review comprehensively examines the various epigenetic regulatory changes in ovarian granulosa cells (OGCs) and oocytes during DOR. DNA methylation plays a crucial role in regulating granulosa cell function, hormone production, and oocyte development, maturation, and senescence. Histone modifications are involved in regulating follicular activation, while non-coding RNAs, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), regulate granulosa cell function and oocyte development. N6-methyladenosine (m6A) modifications are associated with age-related oocyte senescence. Epigenetic clocks based on DNA methylation show potential in predicting ovarian reserve in DOR. Furthermore, it discusses the potential for utilizing epigenetic mechanisms to better diagnose and manage DOR.