PMID- 33744484 OWN - NLM STAT- MEDLINE DCOM- 20210426 LR - 20210426 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 152 DP - 2021 Jul TI - Environmental exposure to per- and polyfluoroalkyl substances mixture and male reproductive hormones. PG - 106496 LID - S0160-4120(21)00121-5 [pii] LID - 10.1016/j.envint.2021.106496 [doi] AB - BACKGROUND: Previous epidemiological studies on the relationship between per- and polyfluoroalkyl substances (PFAS) exposure and male reproductive hormones were mainly limited to a few legacy PFAS and ignored the possible mixture effects. OBJECTIVES: To assess the associations of PFAS mixture, branched isomers and emerging alternatives of PFAS with male reproductive hormones. METHODS: A total of 902 men (mean age: 31.3 years) were recruited in this cross-sectional study. We quantified 24 targeted PFAS, including 7 branched PFOS isomers, 2 branched PFOA isomers and 2 components of F-53B, in blood plasma. Five reproductive hormones, including total testosterone (TT), estradiol (E(2)), follicular stimulating hormone (FSH), luteinizing hormone (LH) and insulin like factor 3 (INSL3), and sex hormone binding globulin (SHBG) were measured in serum. Associations were first assessed by confounder-adjusted multiple linear regression while correcting for multiple comparisons. Bayesian kernel machine regression (BKMR) and adaptive elastic net (AENET) were further used to assess mixture effects and the adjusted exposure response (ER) relationship of individual PFAS. RESULTS: After adjusting for confounders, we found that PFAS mixture was significantly and inversely associated with E(2) and E(2)/TT, with perfluoro-n-undecanoic acid (PFuDA) being the major contributor. Although the associations between PFAS mixture and other hormones were non-significant, certain individual PFAS presented significant associations. Notably, perfluoro-n-tridecanoic acid (PFTrDA) and perfluoro-n-dodecanoic acid (PFDoA) were found to be significantly and inversely associated with INSL3, a unique indicator of Leydig cells function. Meanwhile, significant positive associations were found between perfluorobutane sulfonic acid (PFBS) and FSH and between PFuDA and LH. But the associations with branched isomers or F-53B were sporadic and inconsistent. CONCLUSIONS: Our findings provided the evidence that PFAS mixture may reduce E(2) level, and certain PFAS (i.e., PFTrDA and PFDoA) may have negative effects on Leydig cells function among young men. Additional studies are much needed to confirm our results and elucidate potential mechanisms. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Luo, Kai AU - Luo K AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. FAU - Liu, Xiaotu AU - Liu X AD - School of Environment, Guangzhou Key Laboratory of Environmental Exposure and Health, and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China. FAU - Nian, Min AU - Nian M AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. FAU - Wang, Yuqing AU - Wang Y AD - Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. FAU - Qiu, Jin AU - Qiu J AD - Center for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Shanghai Human Sperm Bank, Shanghai 200135, China. FAU - Yu, Hao AU - Yu H AD - School of Environment, Guangzhou Key Laboratory of Environmental Exposure and Health, and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China. FAU - Chen, Xiangfeng AU - Chen X AD - Center for Reproductive Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Shanghai Human Sperm Bank, Shanghai 200135, China. Electronic address: allanbacon@163.com. 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 200025, China; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: junjimzhang@sina.com. CN - Shanghai Birth Cohort LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210318 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Alkanesulfonic Acids) RN - 0 (Environmental Pollutants) RN - 0 (Fluorocarbons) RN - 0 (Sulfonic Acids) SB - IM MH - Adult MH - *Alkanesulfonic Acids MH - Bayes Theorem MH - Cross-Sectional Studies MH - Environmental Exposure MH - *Environmental Pollutants/toxicity MH - *Fluorocarbons/toxicity MH - Humans MH - Male MH - Sulfonic Acids OTO - NOTNLM OT - Estradiol OT - Insulin-like factor 3 (INSL3) OT - Mixture effects OT - Per- and polyfluoroalkyl substances OT - Young adult men EDAT- 2021/03/22 06:00 MHDA- 2021/04/27 06:00 CRDT- 2021/03/21 20:58 PHST- 2020/11/25 00:00 [received] PHST- 2021/01/28 00:00 [revised] PHST- 2021/02/28 00:00 [accepted] PHST- 2021/03/22 06:00 [pubmed] PHST- 2021/04/27 06:00 [medline] PHST- 2021/03/21 20:58 [entrez] AID - S0160-4120(21)00121-5 [pii] AID - 10.1016/j.envint.2021.106496 [doi] PST - ppublish SO - Environ Int. 2021 Jul;152:106496. doi: 10.1016/j.envint.2021.106496. Epub 2021 Mar 18.