Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid

Chang Gao, Nan Sun, Jinying Xie, Jiehao Li, Lin Tao, Lijuan Guo, Lan Shi, Xiaojin He, Xiaoting Shen, Hua Wang, Pan Yang, Adrian Covaci, Yichao Huang

Department of Toxicology, School of Public Health, Center for Big Data and Population Health of IHM, Key Laboratory of Environmental Toxicology of Anhui Higher
Education Institutes, MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, China; Department of Public Health and Preventive Medicine, China Greater Bay Area Research Center of Environmental Health, School of Medicine, Jinan University, Guangzhou, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, Anhui Province, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Toxicological Center, University of Antwerp, Wilrijk, Belgium; Clinical Research Center, Suzhou Hospital of Anhui Medical University, Anhui Medical University, Suzhou, China.

Abstract: Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (β = − 0.18, 95%CI: − 0.29 – − 0.07, P = 0.002) and progressive motility (β = − 0.27, 95%CI: − 0.43 – − 0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main
effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: β = 0.26, 95% CI: 0.01 – − 0.51, Pinteraction = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 – 1.05, Pinteraction = 0.003). Coexposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm
quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

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Environment International – https://repository.uantwerpen.be/docman/irua/49d3b2motoM1a
Received 27 January 2024; Received in revised form 5 March 2024; Accepted 7 March 2024