精液金属元素混合暴露对精液质量的影响，总抗氧化能力的中介作用，以及中国生育期男性 GSTM1/GSTT1 基因缺失的调节作用。
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.
机构信息
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.
Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
出版信息
Environ Res. 2023 Jul 15;229:115888. doi: 10.1016/j.envres.2023.115888. Epub 2023 Apr 11.
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 (β[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.
背景
金属暴露对精液质量的影响以及氧化损伤在此过程中的作用尚不清楚。
方法
我们招募了 825 名中国男性志愿者，检测了 12 种精液金属（Mn、Cu、Zn、Se、Ni、Cd、Pb、Co、Ag、Ba、Tl 和 Fe）、总抗氧化能力（TAC）和还原型谷胱甘肽的水平。还检测了精液参数和 GSTM1/GSTT1 缺失基因型。应用贝叶斯核机器回归（BKMR）评估混合金属暴露对精液参数的影响。分析 TAC 的中介作用和 GSTM1/GSTT1 缺失的调节作用。
结果
大多数精液金属浓度相互关联。BKMR 模型显示精液体积与金属混合物呈负相关，其中 Cd（cPIP = 0.60）和 Mn（cPIP = 0.10）是主要贡献者。与将所有标准化金属固定在中位数（第 50 个百分位数）相比，将标准化金属固定在第 75 个百分位数可使 TAC 降低 2.17 个单位（95%CI：-2.60，-1.75）。中介分析表明，Mn 降低了精液体积，其中 27.82%的关联由 TAC 介导。BKMR 和多元线性模型均显示，精液 Ni 与精子浓度、总精子数和前向运动精子呈负相关，而这种相关性受 GSTM1/GSTT1 调节。此外，在 GSTT1 和 GSTM1 缺失的男性中，Ni 和总精子数呈负相关（β[95%CI]：0.328 [-0.521，-0.136]），而在 GSTT1 和/或 GSTM1 存在的男性中则没有。虽然 Fe 与精子浓度和总精子数呈正相关，但在单变量分析中呈反“U”形。
结论
暴露于 12 种金属与精液体积呈负相关，其中 Cd 和 Mn 是主要贡献者。TAC 可能介导这一过程。GSTM1 和 GSTM1 可调节精液 Ni 暴露导致的总精子数减少。
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