Bhingardeve Snehal, Sagvekar Pooja, Mukherjee Srabani
Department of Molecular Endocrinology, National Institute for Research in Reproductive and Child Health, Parel, Mumbai, India.
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Reprod Biomed Online. 2025 Jul;51(1):104838. doi: 10.1016/j.rbmo.2025.104838. Epub 2025 Jan 23.
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrinopathy affecting women of reproductive age. This multifactorial disorder is characterized by oligo- or amenorrhoea, clinical and biochemical signs of hyperandrogenism, polycystic ovarian morphology on ultrasound, and impaired fertility. Beyond reproductive challenges, PCOS is associated with elevated risks of metabolic disturbances and associated comorbidities including insulin resistance, obesity, hypertension, type 2 diabetes and cardiovascular diseases. Despite extensive research, the pathophysiology of PCOS remains elusive. Advances in high-throughput sequencing and molecular biology techniques reflect the tandem influence of both genetic and epigenetic factors in its pathogenesis. Notably, the absence of strong genetic determinants and growing evidence implicating intrauterine and lifestyle-associated factors strongly support the epigenetic model of inheritance and development of PCOS. The epigenetic machinery, through mechanisms including DNA and RNA methylation and histone modifications, regulates gene expression and chromatin structure. Recent studies have identified small non-coding RNA and particularly microRNAs (miRNAs) as additional epigenetic components that modulate transcriptional silencing by interacting with target mRNA. Together, these epigenetic mechanisms impact tissue-specific gene expression patterns and, hence, potential to trigger disease development. Changes in global and tissue-specific DNA methylation and miRNA expression patterns have been studied extensively in the context of the pathophysiology of PCOS. Many of these changes have been linked to metabolic and ovarian dysregulation associated with this condition. This review highlights recent advances in understanding the epigenetic landscape of PCOS, focusing on DNA methylation and changes in miRNA expression, and discusses their implications on mechanisms underlying the development of PCOS.
多囊卵巢综合征（PCOS）是一种影响育龄女性的复杂且异质性的内分泌疾病。这种多因素疾病的特征为月经稀发或闭经、高雄激素血症的临床和生化体征、超声检查显示多囊卵巢形态以及生育能力受损。除了生殖方面的挑战，PCOS还与代谢紊乱及相关合并症的风险升高有关，包括胰岛素抵抗、肥胖、高血压、2型糖尿病和心血管疾病。尽管进行了广泛研究，但PCOS的病理生理学仍不明确。高通量测序和分子生物学技术的进展反映了遗传和表观遗传因素在其发病机制中的协同影响。值得注意的是，缺乏强大的遗传决定因素以及越来越多涉及子宫内和生活方式相关因素的证据，有力地支持了PCOS遗传和发育的表观遗传模型。表观遗传机制通过DNA和RNA甲基化以及组蛋白修饰等机制调节基因表达和染色质结构。最近的研究已将小非编码RNA，特别是微小RNA（miRNA）确定为通过与靶mRNA相互作用来调节转录沉默的额外表观遗传成分。这些表观遗传机制共同影响组织特异性基因表达模式，从而影响引发疾病发展的可能性。在PCOS的病理生理学背景下，已经广泛研究了全基因组和组织特异性DNA甲基化以及miRNA表达模式的变化。其中许多变化与该疾病相关的代谢和卵巢功能失调有关。本综述重点介绍了在理解PCOS表观遗传学格局方面的最新进展，着重于DNA甲基化和miRNA表达变化，并讨论了它们对PCOS发病机制的影响。
