Epigenetic Regulation in Polycystic Ovarian Syndrome: Mechanisms, Environmental Interactions, and Therapeutic Perspectives

Polycystic ovary syndrome (PCOS), which has recently been proposed to be renamed polyendocrine metabolic ovarian syndrome (PMOS), is a reproductive endocrine-metabolic disorder affecting women of reproductive age. It is clinically characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently accompanied by metabolic abnormalities, including insulin resistance and obesity. Despite extensive investigation, the pathogenesis of PCOS remains complex and incompletely understood. Increasing evidence indicates that epigenetic modifications play a critical role in the initiation and progression of PCOS. Epigenetic mechanisms, including DNA methylation, histone modifications, and the regulation of non-coding RNAs, modulate gene expression without altering the underlying DNA sequence and thereby contribute to pathological processes such as ovarian dysfunction, hormonal imbalance, and metabolic dysregulation. This review summarizes current research on the association between epigenetic modifications and PCOS. It focuses on aberrant DNA methylation of genes involved in steroid hormone synthesis and metabolic regulation that contribute to hyperandrogenemia and insulin resistance; histone modifications, such as acetylation and methylation, which alter chromatin structure and regulate the transcription of genes essential for follicular development, leading to ovulatory disorders; and non-coding RNAs, including microRNAs and long non-coding RNAs, which further exacerbate the PCOS phenotype by targeting key genes involved in hormone biosynthesis and insulin signaling pathways. In addition, environmental factors, such as the intrauterine environment and exposure to endocrine-disrupting chemicals, can induce abnormal epigenetic modifications and interact with genetic susceptibility, thereby increasing the risk of PCOS. A comprehensive understanding of epigenetic mechanisms in PCOS not only provides new insights into its etiology but also lays a theoretical foundation for the development of diagnostic biomarkers and therapeutic strategies based on epigenetic regulation.