同时暴露于 55 种内分泌干扰化学物质与精子质量下降有关：混合物效应，以及精浆 docosapentaenoic 酸的作用。

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

机构信息

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.

出版信息

Environ Int. 2024 Mar;185:108571. doi: 10.1016/j.envint.2024.108571. Epub 2024 Mar 11.

DOI:10.1016/j.envint.2024.108571

PMID:38471262

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, P = 0.047; progressive motility: β = 0.64, 95%CI: 0.23 - 1.05, P = 0.003). Co-exposure 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.

摘要

已广泛研究了单一内分泌干扰化学物质（EDC）对男性生殖健康的孤立影响，但它们的混合物效应仍不清楚。先前的研究表明，食用富含ω-3 多不饱和脂肪酸（PUFA）的饮食可能对生殖健康有益，但ω-3 PUFA 是否可以调节 EDC 混合物对精液质量的影响仍有待探索。在这项在中国一家生殖健康中心招募的 155 名男性的研究中，我们使用靶向暴露组学同时测量尿液中的 55 种 EDC 以评估暴露负担。回归分析仅限于高检出 EDC（≥55%，n=34），并且进一步筛选出那些具有一致升高风险的 EDC，并将其纳入混合物效应模型（双酚 A、乙基对羟基苯甲酸酯、甲基对羟基苯甲酸酯[MeP]、二苯甲酮-1[BP1]、二苯甲酮-3、单（3-羧丙基）邻苯二甲酸酯[MCPP]）。贝叶斯核机器回归（BKMR）和基于分位数的 g 计算（QGC）模型表明，排名靠前的 EDC 的共同暴露与精子总数（β=-0.18，95%CI：-0.29--0.07，P=0.002）和前向运动能力（β=-0.27，95%CI：-0.43--0.10，P=0.002）降低有关，但与精液量减少无关。使用混合物模型分析发现，BP1、MeP 和 MCPP 是精子运动参数恶化的主要效应驱动因素。精液等离子体脂肪酸分析表明，高水平的ω-3 PUFA，特别是二十二碳五烯酸（DPA，C22：5n-3）水平升高，可调节 MCPP 与精子运动参数之间的关联（总活力：β=0.26，95%CI：0.01--0.51，P=0.047；前向运动能力：β=0.64，95%CI：0.23--1.05，P=0.003）。一系列 EDC 的共同暴露主要与精子质量恶化有关，但在一定程度上与精子数量减少有关，高水平的精液 DPA 状态可能对这种影响具有保护作用。我们的工作强调了暴露组学方法评估化学暴露的重要性，并强调了一种新的可能干预目标，以减轻 EDC 对精液质量的潜在不良影响。