University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States.
University of Michigan School of Public Health, Department of Biostatistics, Ann Arbor, MI, United States.
Sci Total Environ. 2024 Jun 10;928:172295. doi: 10.1016/j.scitotenv.2024.172295. Epub 2024 Apr 7.
BACKGROUND/AIM: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort.
We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms.
A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb (β:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (β:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex-specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex-specific associations with Cs were inverse among females, while significant sex-specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group.
Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metal-induced adverse birth outcomes.
背景/目的：重金属已知会引起氧化应激和炎症，金属暴露与不良出生结局之间的关联已得到充分证实。然而，关于将金属暴露与不良出生结局联系起来的生物标志物谱的研究还很缺乏。类二十烷酸是调节体内炎症的脂质分子，越来越多的证据表明，血浆类二十烷酸与妊娠结局之间存在关联。类二十烷酸可能有助于我们理解病因性分娩途径。在这里，我们评估了 654 名波多黎各 PROTECT 出生队列孕妇在妊娠中期 18 周和 26 周时采集的全血中 11 种金属浓度与血浆中类二十烷酸谱之间的关联。使用多元线性模型将类二十烷酸回归到金属浓度上。通过交互项探索了婴儿性别对效应的修饰作用。
我们测量了中位数为 18 周和 26 周妊娠时采集的全血中的 11 种金属浓度和中位数为 26 周时采集的血浆中的类二十烷酸谱。使用多元线性模型将类二十烷酸回归到金属浓度上。通过交互项探索了婴儿性别对效应的修饰作用。
共分析了 55 种类二十烷酸。值得注意的是，12-氧代二十碳四烯酸（12-氧代 ET E）和 15-氧代二十碳四烯酸（15-氧代 ET E），这两种物质都具有炎症活性，与金属浓度的关联最多。这些类二十烷酸与 Cu、Mn 和 Zn 的浓度增加有关，与 Cd、Co、Ni 和 Pb 的浓度降低有关，12-氧代 ET E 和 Pb（β：-33.5，95%CI：-42.9，-22.6）和 15-氧代 ET E 和 Sn（β：43.2，95%CI：11.4，84.1）的效应量最大。此外，我们还观察到了金属-类二十烷酸关联因婴儿性别而异。特别是，Cs 和 Mn 与类二十烷酸的关联在婴儿性别特异性方面最为显著，这主要是由女性胎儿驱动的。Cs 与女性之间的所有显著性别特异性关联均为负相关，而 Mn 与女性之间的显著性别特异性关联在环氧化酶组中为正相关，但在脂氧化酶组中为负相关。
某些金属与负责调节炎症反应的类二十烷酸显著相关。类二十烷酸-金属关联可能表明类二十烷酸在介导金属诱导的不良出生结局方面发挥作用。
