Per- and polyfluoroalkyl substances exposure and endometriosis risk: Evidence from epidemiologic, network toxicology, and molecular docking

Haiqiao Zhang, Siliang Zeng, Jingyun Yu, Fengming Zhu, Faming Zhu, Xiandan Yang, Weichao He, Weihua He, Yuwei Liu, Yu Liang, Yang Liang, Liang Yang, Wenxin Hong, 謙一 松原, Qian Yuan
iScience · 2025 · vol. 28(12) , pp. 114145 · doi:10.1016/j.isci.2025.114145 · PMID:41492385 · PMC12765064 · W4416426323
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

PFAS mixtures are associated with increased endometriosis risk, with PFOA and PFOS being major contributors, potentially through endocrine disruption and inflammation via steroid hormone signaling and PI3K-Akt pathways.

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Abstract

Although per- and polyfluoroalkyl substances (PFAS) exposure has been linked to endometriosis, this association remains controversial, and the underlying mechanisms are unclear. This study aimed to investigate this relationship and explore its molecular basis. Using cross-sectional data from NHANES, we analyzed serum PFAS in 1,069 women (20-50 years), applying WQS and BKMR models to assess mixture effects. Network toxicology (protein-protein interaction, pathway enrichment), molecular docking, and external validation were also used. Results showed PFAS mixtures were positively associated with endometriosis (adjusted OR = 1.22, 95% CI: 1.08-1.39), with PFOA and PFOS as main contributors. Mechanistic analysis revealed 129 overlapping genes involved in steroid hormone signaling, inflammatory responses, and the PI3K-Akt pathway, along with potential disruptions in lipid metabolism and oxidative stress. This work provides epidemiological and mechanistic evidence that PFAS mixtures may promote endometriosis via endocrine disruption and inflammatory activation, highlighting the need for further research into their gynecological health effects.

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endometriosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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