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Endocrine-disrupting chemicals and polycystic ovary syndrome: A systems toxicology perspective on mechanistic pathways.

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Reproductive toxicology (Elmsford, N.Y.) 2026 Vol.142() p. 109233 OA Ovarian function and disorders
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PubMed DOI OpenAlex 마지막 보강 2026-04-29
OpenAlex 토픽 · Ovarian function and disorders Reproductive Biology and Fertility Effects and risks of endocrine disrupting chemicals

Zhu XJ, Xu W, Lu AF

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This review presents a novel conceptual framework-the Multi-Hit, Multi-Level Cascade Model-that systematically integrates evidence from systems toxicology, molecular endocrinology, and epidemiology.

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APA Xiao-Juan Zhu, Wenting Xu, Ai-Fang Lu (2026). Endocrine-disrupting chemicals and polycystic ovary syndrome: A systems toxicology perspective on mechanistic pathways.. Reproductive toxicology (Elmsford, N.Y.), 142, 109233. https://doi.org/10.1016/j.reprotox.2026.109233
MLA Xiao-Juan Zhu, et al.. "Endocrine-disrupting chemicals and polycystic ovary syndrome: A systems toxicology perspective on mechanistic pathways.." Reproductive toxicology (Elmsford, N.Y.), vol. 142, 2026, pp. 109233.
PMID 41912123 ↗

Abstract

This review presents a novel conceptual framework-the Multi-Hit, Multi-Level Cascade Model-that systematically integrates evidence from systems toxicology, molecular endocrinology, and epidemiology. Our model posits that chronic exposure to real-world EDC mixtures initiates a cascade of events wherein cellular perturbations (oxidative stress and low-grade inflammation) are amplified within the uniquely vulnerable ovarian microenvironment. This cascade then escalates into a systemic, self-perpetuating metabolic-endocrine-inflammatory vicious cycle, ultimately manifesting as the diverse clinical phenotypes of PCOS. Within this model, we formally propose three novel, testable hypotheses: the PCOS-specific vulnerability hypothesis, the cumulative susceptibility window hypothesis, and the mixture-driven synergistic toxicity hypothesis. By integrating fragmented evidence into a cohesive narrative, this framework not only provides a mechanistic understanding of EDC-induced PCOS pathogenesis but also identifies critical knowledge gaps and charts a roadmap for future research and targeted prevention strategies.

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