Per- and polyfluoroalkyl substances (PFAS) Induced Epigenetic Dysregulation in Endometriosis: A Mechanistic Review

Endometriosis is a chronic estrogen-dependent inflammatory disorder characterized by the ectopic growth of endometrial-like tissue and associated with pelvic pain, infertility, and impaired quality of life. Although its pathogenesis is multifactorial, increasing evidence suggests that environmental toxicants may contribute to disease development and progression through epigenetic mechanisms. Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with recognized endocrine-disrupting, immunomodulatory, and oxidative stress inducing properties. Recent epidemiological and toxicological studies have reported associations between PFAS exposure and endometriosis, particularly in relation to disease severity and progression. This mechanistic review examines current evidence linking PFAS exposure to epigenetic dysregulation in endometriosis by integrating epidemiological, molecular, and toxicological findings. Particular emphasis is done on DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation as potential mediators of PFAS-induced reproductive toxicity. Available evidence suggests that PFAS-associated epigenetic alterations may disrupt steroid hormone signaling, immune surveillance, inflammatory pathways, angiogenesis, and fibrotic remodeling, thereby contributing to endometriosis pathophysiology. An integrative mechanistic framework is proposed to explain how chronic PFAS exposure may influence disease susceptibility and progression. Further investigation of these mechanisms may improve understanding of environmentally mediated reproductive toxicity and aid identification of potential epigenetic biomarkers in endometriosis.