PMID- 37054833 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20230522 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 229 DP - 2023 Jul 15 TI - Mixed exposure effect of seminal metals on semen quality, mediation of total antioxidant capacity, and moderation of GSTM1/GSTT1 gene deletion in Chinese reproductive-aged men. PG - 115888 LID - S0013-9351(23)00680-1 [pii] LID - 10.1016/j.envres.2023.115888 [doi] AB - BACKGROUND: The effects of metal exposure on semen quality and the role of oxidative damage in this process remain unclear. METHODS: We recruited 825 Chinese male volunteers, and 12 seminal metals (Mn, Cu, Zn, Se, Ni, Cd, Pb, Co, Ag, Ba, Tl, and Fe), the total antioxidant capacity (TAC), and reduced glutathione were measured. Semen parameters and GSTM1/GSTT1-null genotypes were also detected. Bayesian kernel machine regression (BKMR) was applied to evaluate the effect of the mixed exposure to metals on semen parameters. The mediation of TAC and moderation of GSTM1/GSTT1 deletion were analyzed. RESULTS: Most seminal metal concentrations were correlated with each other. The BKMR models revealed a negative association between the semen volume and metal mixture, with Cd (cPIP = 0.60) and Mn (cPIP = 0.10) as the major contributors. Compared to fixing all scaled metals at their median value (50th percentiles), fixing the scaled metals at their 75th percentiles decreased the TAC by 2.17 units (95%CI: -2.60, -1.75). Mediation analysis indicated that Mn decreased the semen volume, with 27.82% of this association mediated by TAC. Both the BKMR and multi-linear models showed that seminal Ni was negatively correlated with sperm concentration, total sperm count, and progressive motility, which was modified by GSTM1/GSTT1. Furthermore, Ni and the total sperm count showed a negative association in GSTT1 and GSTM1 null males (beta[95%CI]: 0.328 [-0.521, -0.136]) but not in males with GSTT1 and/or GSTM1. Although Fe and the sperm concentration and total sperm count were positively correlated, they showed inverse "U" shapes in univariate analysis. CONCLUSION: Exposure to the 12 metals was negatively associated with semen volume, with Cd and Mn as the major contributors. TAC may mediate this process. GSTT1 and GSTM1 can modify the reduction in the total sperm count caused by seminal Ni exposure. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Ren, Jingchao AU - Ren J AD - School of Public Health and Management, Chongqing Medical University, Chongqing, 400038, China; Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Jin, Huidong AU - Jin H AD - Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China. FAU - Zhang, Chen AU - Zhang C AD - Institute of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200032, China; Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China. FAU - Liu, Song AU - Liu S AD - Reproductive Medicine Centre, Maternal and Child Health Care Hospital of Shandong Province, Jinan, 250014, China. FAU - Han, Yufen AU - Han Y AD - Puyang Maternity and Child Care Centers, 59 South Section of Kaizhou Road, Puyang, 457000, China. FAU - Xi, Jinyan AU - Xi J AD - Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Cao, Jinhu AU - Cao J AD - Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Lin, Fenglong AU - Lin F AD - Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Zhang, Pingyang AU - Zhang P AD - Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Zhang, Fengquan AU - Zhang F AD - Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China. FAU - Zhang, Guang-Hui AU - Zhang GH AD - Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China. FAU - Yang, Huijun AU - Yang H AD - Reproductive Medicine Centre, Maternal and Child Health Care Hospital of Shandong Province, Jinan, 250014, China. Electronic address: lwyhj@163.com. FAU - Huang, Hefeng AU - Huang H AD - Institute of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200032, China; Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China. Electronic address: huanghefg@hotmail.com. FAU - Cao, Jia AU - Cao J AD - Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: caojia1962@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230411 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Antioxidants) RN - 00BH33GNGH (Cadmium) RN - 0 (Metals) RN - EC 2.5.1.18 (glutathione S-transferase M1) RN - EC 2.5.1.- (glutathione S-transferase T1) RN - EC 2.5.1.18 (Glutathione Transferase) RN - 42Z2K6ZL8P (Manganese) SB - IM MH - Adult MH - Humans MH - Male MH - *Antioxidants MH - Bayes Theorem MH - Cadmium MH - East Asian People MH - Gene Deletion MH - Metals/toxicity MH - Semen MH - *Semen Analysis MH - *Glutathione Transferase/genetics MH - Manganese OTO - NOTNLM OT - Bayesian kernel machine regression OT - GSTM1 OT - GSTT1 OT - Metal OT - Sperm OT - Total antioxidant capacity COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/14 06:00 MHDA- 2023/05/22 06:42 CRDT- 2023/04/13 19:22 PHST- 2023/02/21 00:00 [received] PHST- 2023/04/06 00:00 [revised] PHST- 2023/04/11 00:00 [accepted] PHST- 2023/05/22 06:42 [medline] PHST- 2023/04/14 06:00 [pubmed] PHST- 2023/04/13 19:22 [entrez] AID - S0013-9351(23)00680-1 [pii] AID - 10.1016/j.envres.2023.115888 [doi] PST - ppublish SO - Environ Res. 2023 Jul 15;229:115888. doi: 10.1016/j.envres.2023.115888. Epub 2023 Apr 11.