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

In: International Journal of Science and Research Archive · 2026 · vol. 19(2) , pp. 741–750 · doi:10.30574/ijsra.2026.19.2.1080 · W7161291422
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This review examines how per- and polyfluoroalkyl substances (PFAS) induce epigenetic dysregulation in endometriosis, potentially contributing to disease pathophysiology through alterations in DNA methylation, histone modification, and non-coding RNAs.

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This mechanistic review examines the potential link between exposure to per- and polyfluoroalkyl substances (PFAS) and epigenetic dysregulation in the pathophysiology of endometriosis. The authors integrate epidemiological, molecular, and toxicological evidence to propose that PFAS-induced alterations in DNA methylation, histone modification, and non-coding RNA may disrupt steroid hormone signaling, immune surveillance, and inflammatory pathways. While acknowledging the multifactorial nature of the disease, the paper suggests these environmental toxicants contribute to disease severity and progression through specific epigenetic mechanisms. This paper is centrally about endometriosis — specifically exploring how environmental contaminants like PFAS may drive disease development via epigenetic changes.

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Abstract

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.
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Department of Zoology, Isabella Thoburn College, Lucknow, India. Shivani Tiwari; ORCID ID: 0009-0001-4612-6149 Newton Paul; ORCID ID: 0000-0001-8288-7458 International Journal of Science and Research Archive, 2026, 19(02), 741-750 Article DOI: 10.30574/ijsra.2026.19.2.1080 Received on 10 April 2026; revised on 10 May 2026; accepted on 12 May 2026 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. Endometriosis; PFAS; Epigenetic dysregulation; Endocrine disruption; DNA methylation; Reproductive toxicology. Preview Article PDF Shivani Tiwari and Newton Paul. Per- and polyfluoroalkyl substances (PFAS) Induced Epigenetic Dysregulation in Endometriosis: A Mechanistic Review. International Journal of Science and Research Archive, 2026, 19(02), 741-750. Article DOI: https://doi.org/10.30574/ijsra.2026.19.2.1080.

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