Liu Nian, Li Guangming, Zhang Guohuan, Li Yu, Meng Tian-Qing, Xiong Cheng-Liang, Pan An, Guo Hua, Li Yingying, Liu Lihong, He Bin, Yin Yongguang, Shi Jianbo, Liang Yong, Wang Yi-Xin, Hu Ligang, Jiang Guibin
School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Environ Health (Wash). 2025 Jun 17;3(9):1083-1093. doi: 10.1021/envhealth.5c00082. eCollection 2025 Sep 19.
Immune modulation is crucial for male reproduction and fertility. Metals and metalloids (metals) have been extensively studied for their immunomodulatory effects. Whether metal exposure affects semen quality through immune modulation is unclear. In the present study, we explored the associations between exogenous metals within immune cells, immune cell proportions, and semen quality among 84 healthy men who repeatedly provided 266 semen samples over 90 days. We employed mass cytometry (CyTOF) technology to identify immune cells in semen and measured exogenous metals in these cells at the single-cell resolution. After adjusting for potential confounders, most detected metals in immune cells were inversely associated with the proportion of immune cells in semen samples (all < 0.05), indicating the adverse effects of exogenous metals on immune cells. The proportion of immune cells showed N-shaped, nonlinear associations with sperm concentration, total count, progressive motility, and total motility. Mediation analyses showed that the percentage of indirect effects of exogenous metals on sperm quality parameters via immune cells ranged from 15.11% to 54.29%. Overall, our findings unravel the indirect effects of exogenous metal exposure on male reproductive health via immune cells, contributing valuable insights into the complex interplay between environmental factors, immune cells, and human semen quality.
免疫调节对男性生殖和生育能力至关重要。金属和类金属（金属）因其免疫调节作用已得到广泛研究。金属暴露是否通过免疫调节影响精液质量尚不清楚。在本研究中，我们探讨了84名健康男性在90天内反复提供266份精液样本时，免疫细胞内的外源性金属、免疫细胞比例与精液质量之间的关联。我们采用质谱流式细胞术（CyTOF）技术识别精液中的免疫细胞，并在单细胞分辨率下测量这些细胞中的外源性金属。在调整潜在混杂因素后，免疫细胞中检测到的大多数金属与精液样本中免疫细胞的比例呈负相关（均P<0.05），表明外源性金属对免疫细胞有不良影响。免疫细胞比例与精子浓度、总数、前向运动率和总运动率呈N形非线性关联。中介分析表明，外源性金属通过免疫细胞对精子质量参数的间接影响百分比在15.11%至54.29%之间。总体而言，我们的研究结果揭示了外源性金属暴露通过免疫细胞对男性生殖健康的间接影响，为环境因素、免疫细胞和人类精液质量之间的复杂相互作用提供了有价值的见解。
