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前瞻性研究孕早期金属混合物与母血和脐血线粒体 DNA 拷贝数及端粒长度的关系。

Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood.

机构信息

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, California, USA.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

出版信息

Environ Health Perspect. 2021 Nov;129(11):117007. doi: 10.1289/EHP9294. Epub 2021 Nov 19.

Abstract

BACKGROUND

Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.

OBJECTIVES

We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.

METHODS

We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn () and TL () in second-trimester maternal blood and mtDNAcn () and TL () in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.

RESULTS

A 2-fold increase in maternal magnesium was associated with lower maternal [, 95% confidence interval (CI): , ] and cord blood (, 95% CI: , ) mtDNAcn. Lead was associated with higher maternal mtDNAcn (, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.

DISCUSSION

Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294.

摘要

背景

孕期金属暴露会影响母婴健康。氧化应激和炎症可能介导重金属的不良影响,而必需金属则可能充当抗氧化剂。线粒体 DNA 是金属诱导氧化损伤的主要靶点。端粒功能障碍归因于活性氧化剂与抗氧化剂之间的失衡。

目的

我们评估了产前金属对母体和脐带血中线粒体 DNA 拷贝数(mtDNAcn)和端粒长度(TL)的个体和联合影响,将其作为炎症和氧化应激的生物标志物。

方法

我们在一项美国产前队列项目 Viva 中测量了孕妇红细胞中的 6 种非必需金属(砷、钡、镉、铯、铅、汞)和 4 种必需金属(镁、锰、硒、锌)。我们测量了母体血液中第二孕期的相对 mtDNAcn()和 TL()以及脐带血中的 mtDNAcn()和 TL()。我们使用多变量线性回归和分位数 g 计算来估计产前金属与生物标志物之间的关联。我们使用广义加性模型和贝叶斯核机器回归来检验非线性和相互作用。

结果

母体镁增加 2 倍与母体[,95%置信区间(CI):,]和脐带血[,95%置信区间(CI):,]mtDNAcn 降低相关。铅与母体 mtDNAcn 升高相关(,95%CI:0.01,0.06)。硒与脐带血 TL 延长相关(,95%CI:0.01 0.50)。非必需金属混合物与较高的母体 mtDNAcn 之间存在关联(,95%CI:0.01,0.07)。脐带血 mtDNAcn 与镁之间存在非线性关系;母体 mtDNAcn 与钡、铅和汞之间存在关系;母体 TL 与钡之间存在关系。

讨论

母体暴露于铅、镁和硒等金属与母体第二孕期和脐带血中的 mtDNAcn 和 TL 相关。未来的工作将评估这些生物标志物是否与儿童健康有关。https://doi.org/10.1289/EHP9294.

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