Background

Although epidemiologic studies have found associations between several chemical biomarkers and semen parameters, only a few studies have evaluated their combined effects and interactions.

Methods

We included 420 men aged 18–55 years who participated in the Environment and Reproductive Health (EARTH) study between 2005 and 2019 at the Massachusetts General Hospital Fertility Center. Four mixture/exposome models, including exposome-wide association studies (ExWAS), Deletion/Substitution/Addition algorithm (DSA), Bayesian Kernel Machine Regression (BKMR), and the non-linear interaction model (NLinteraction), were used to evaluate associations between 24 chemical biomarkers (urinary bisphenol A, four parabens, triclosan, 17 phthalate metabolites, and hair mercury [Hg]) and semen parameters (sperm count, concentration, morphology, motility, and semen volume).

Results

Overall, Hg was positively, and triclosan was negatively significantly associated with all semen outcomes except semen volume across multiple models. In BKMR, when increasing the mixture from the 10th to 90th percentile, the chemical mixture was negatively associated with percent normal sperm morphology (−1.42 %, 95 % Credibility Interval [CRI] −12.36; 9.52), motility (−0.10 %, 95 % CRI −1.78; 1.58), and volume (−0.26 mL, 95 % CRI −0.79; 0.28), and positively associated with sperm count (0.21 mill, 95 % CRI −0.23; 0.65) and concentration (0.33 mill/mL, 95 % CRI −0.14; 0.80). We detected one interaction between urinary triclosan and butylparaben in relation to normal sperm morphology using NLinteraction.

Conclusion

Among 24 biomarkers tested, Hg and triclosan showed consistent associations with semen parameters while other biomarkers were less consistent depending on the model used. Similar research studies should be encouraged to use multiple models to incorporate interaction assessment and assess the robustness of results.

中文翻译：

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使用混合物和暴露组方法评估化学生物标志物与精液参数的关联和相互作用

  背景

尽管流行病学研究发现几种化学生物标志物与精液参数之间存在关联，但只有少数研究评估了它们的综合效应和相互作用。

  方法

我们纳入了 420 名年龄在 18-55 岁之间的男性，他们于 2005 年至 2019 年期间在马萨诸塞州总医院生育中心参加了环境与生殖健康 （EARTH） 研究。四种混合物/暴露组模型，包括暴露组范围关联研究 （ExWAS）、缺失/替换/添加算法 （DSA）、贝叶斯核机回归 （BKMR） 和非线性交互模型 （NLinteraction），用于评估 24 种化学生物标志物 （尿双酚 A、四种对羟基苯甲酸酯、三氯生、17 种邻苯二甲酸酯代谢物和头发汞 [Hg]）与精液参数 （精子数量、浓度、形态、活力和精液量） 之间的关联。

  结果

总体而言，Hg 呈正相关，而三氯生与除多个模型中的精液量外的所有精液结局呈负显著相关。在 BKMR 中，当混合物从第 10 个百分位数增加到第 90 个百分位数时，化学混合物与正常精子形态百分比（-1.42%，95% 可信区间 [CRI]-12.36;9.52）、活力（-0.10%、95% CRI -1.78;1.58）和体积（-0.26 mL，95 % CRI -0.79;0.28）呈负相关，并与精子数量（0.21 mill，95 % CRI -0.23;0.65）和浓度（0.33 mill/mL、 95 % CRI −0.14;我们使用 NL 相互作用检测到尿三氯生和对羟基苯甲酸丁酯之间的一种相互作用与正常精子形态有关。

  结论

在测试的 24 种生物标志物中，Hg 和三氯生与精液参数显示出一致的关联，而其他生物标志物则不太一致，具体取决于所使用的模型。应鼓励类似的研究使用多个模型来整合交互评估并评估结果的稳健性。