Epigenetic mechanisms in Polycystic Ovary Syndrome: DNA methylation, Histone modification, and miRNA regulation

Abstract

Polycystic ovary syndrome (PCOS) affects about 10% of reproductive-age women and is characterised by hormonal imbalance, irregular ovulation, and cyst-like follicles in the ovaries. Common features include high androgen levels, insulin resistance, weight gain, and abnormal lipid patterns. Symptoms can vary depending on environmental and geographic factors. Recent studies show that epigenetic changes—modifications in gene activity without altering DNA sequence—play a key role in PCOS. These include DNA methylation, chromatin remodelling, and small regulatory RNAs that control gene expression. Disruptions in these mechanisms can switch genes on or off, affecting ovarian function, egg maturation, metabolism, and immune responses. Women with PCOS often exhibit abnormal DNA methylation in ovarian tissues, particularly in genes such as CYP19A1 and INSR, which are involved in hormone regulation and insulin signalling. Changes in DNA packaging can also disturb ovarian cycles and androgen production. MicroRNAs such as miR-21, miR-93, and miR-222 further regulate follicle growth, insulin action, and hormone secretion. Environmental factors like diet, obesity, early hormone exposure, and endocrine disruptors influence these gene expression changes, contributing to varied symptoms. Emerging treatments, including metformin and other targeted therapies, aim to regulate these molecular pathways. This may allow personalised treatment approaches, improving both metabolic health and reproductive outcomes in individuals with PCOS.