PMID- 37134253 OWN - NLM STAT- MEDLINE DCOM- 20230505 LR - 20230519 IS - 1552-9924 (Electronic) IS - 0091-6765 (Print) IS - 0091-6765 (Linking) VI - 131 IP - 5 DP - 2023 May TI - Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis. PG - 57001 LID - 10.1289/EHP11814 [doi] LID - 057001 AB - BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. OBJECTIVES: This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture. METHODS: From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners. RESULTS: After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, 1m-PFOS, Sigma3,4,5m-PFOS), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [adjusted odds ratio (aOR) = 1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Sigma3,4,5m-PFOS, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. CONCLUSIONS: In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, Sigma3,4,5m-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814. FAU - Zhan, Wenqiang AU - Zhan W AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qiu, Wei AU - Qiu W AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ao, Yan AU - Ao Y AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhou, Wei AU - Zhou W AD - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. AD - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China. FAU - Sun, Yun AU - Sun Y AD - Center for Reproductive Medicine, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhao, Han AU - Zhao H AD - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. AD - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China. FAU - Zhang, Jun AU - Zhang J AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20230503 PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 0 (ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate) RN - 9H2MAI21CL (perfluorooctane sulfonic acid) RN - 0 (Fluorocarbons) RN - P6G1J7NM2D (perfluorododecanoic acid) RN - FX3WJ41CMX (perflexane) RN - 0 (Alkanesulfonic Acids) RN - 0 (Alkanesulfonates) RN - 0 (Environmental Pollutants) SB - IM MH - Humans MH - Female MH - *Polycystic Ovary Syndrome/epidemiology MH - Case-Control Studies MH - Bayes Theorem MH - Overweight MH - *Fluorocarbons MH - Environmental Exposure MH - *Alkanesulfonic Acids/analysis MH - *Infertility MH - Alkanesulfonates/analysis MH - Obesity MH - *Environmental Pollutants PMC - PMC10156134 EDAT- 2023/05/03 18:41 MHDA- 2023/05/05 06:42 PMCR- 2023/05/03 CRDT- 2023/05/03 15:13 PHST- 2023/05/05 06:42 [medline] PHST- 2023/05/03 18:41 [pubmed] PHST- 2023/05/03 15:13 [entrez] PHST- 2023/05/03 00:00 [pmc-release] AID - EHP11814 [pii] AID - 10.1289/EHP11814 [doi] PST - ppublish SO - Environ Health Perspect. 2023 May;131(5):57001. doi: 10.1289/EHP11814. Epub 2023 May 3.