Epigenetic Mechanisms of Reproductive Dysfunction Induced by Endocrine-Disrupting Chemicals: Evidence From Molecular Studies
Seonhwa Hwang, Hyun Bon Kang, Dae Hyun Kim, M. PARK
Abstract
Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, organochlorine pesticides, and heavy metal ions, pose serious threats to reproductive health by interfering with hormonal balance and molecular signaling pathways. Recent research had expanded our understanding of these compounds has beyond their traditional role in hormone receptor interference. EDCs can trigger lasting epigenetic changes, including abnormal DNA methylation, histone modifications, RNA methylation, and altered regulation of non-coding RNA, which can impair reproductive functions such as gametogenesis, folliculogenesis, steroidogenesis, and embryo implantation. Importantly, EDC-mediated epigenetic alterations have been linked to various reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis, reduced ovarian reserve, and impaired spermatogenesis. For example, BPA exposure alters DNA methylation in estrogen signaling and aromatase gene expression, whereas phthalates disrupt histone acetylation and methylation in hormone synthesis pathways. Similarly, pesticides and heavy metal ions may influence microRNA expression and histone structure, further disrupting endocrine-regulated gene networks. These alterations may occur during sensitive developmental windows and can lead to long-term or transgenerational effects on reproductive health. Understanding how EDCs exert their toxicity through epigenetic mechanisms is essential for early detection of exposure, identification of molecular biomarkers, and development of targeted therapies to reduce reproductive risks. Here, we discuss the emerging molecular evidence that provides a comprehensive overview of how EDCs impair reproductive health through epigenetic pathways, thereby offering a framework for future research and translational applications.