Epigenetic regulation by DNA methylation in PCOS and POI: mechanisms of ovarian dysfunction and implications for clinical research

Ovulation disorders are the leading cause of female infertility, primarily due to abnormal regulation of the hypothalamic-pituitary-ovarian (HPO) axis or dysfunction of target organs. The most common conditions in this category are polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI), with the core mechanisms involving follicular developmental abnormalities and impaired oocyte quality. However, the pathophysiological mechanisms underlying PCOS and POI are not yet fully understood. Recent studies have shown that epigenetic regulatory mechanisms play a crucial role in the pathological processes of PCOS and POI, with DNA methylation key epigenetic modification emerging as a focal point of research. Aberrant DNA methylation regulation has been closely linked to follicular developmental disorders and endocrine dysfunction in reproduction. Although research on the role of DNA methylation in PCOS/POI pathology is still in its early stages, it has already demonstrated significant potential as a key epigenetic target. In this study, we comprehensively review the relationship between DNA methylation abnormalities and the pathogenesis of PCOS/POI, exploring their mechanisms of action. We also discuss new research directions and potential epigenetic biomarkers for treating associated comorbidities and improving the quality of life in female patients with ovarian dysfunction. This provides a theoretical foundation for advancing epigenetic diagnostic marker screening, targeted intervention strategies, and accelerating the translation of epigenetic regulatory mechanisms into clinical diagnostic and therapeutic applications.