Individual and mixtures of metal exposures in associations with biomarkers of oxidative stress and global DNA methylation among pregnant women

Background: Prenatal exposure to metals has been linked with adverse pregnancy outcomes. Oxidative stress and epigenetic changes are potential mechanisms of action. Objectives: We aimed to examine the associations of individual and mixtures of metal exposures with oxidative stress and DNA methylation among pregnant women. Methods: We measured a panel of 16 metals and 3 oxidative stress biomarkers including 8-hydroxydeoxyguano-sine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-isoprostaglandin F2 alpha (8-isoPGF2 alpha) in urine from 113 pregnant women in a Chinese cohort. Biomarkers of global DNA methylation including Alu and long interspersed nucleotide element-1 (LINE-1) in cord blood were measured. Multivariable linear regression and Bayesian kernel machine regression (BKMR) models were separately applied to estimate the associations between individual and mixtures of metal exposures and biomarkers of oxidative stress and global DNA methylation. Results: In single-metal analyses, we observed positive associations between 11 metals [arsenic (As), cadmium (Cd), thallium (Tl), barium (Ba), nickel (Ni), vanadium (V), cobalt (Co), zinc (Zn), copper (Cu), selenium (Se) and molybdenum (Mo)] and at least one of oxidative stress biomarkers (all FDR-adjusted P-values < 0.05). In mixture analyses, we found positive overall associations of metal mixtures with 8-OHdG and 8-isoPGF2 alpha, and Se was the most important predictor. There was no evidence on associations of urinary metals as individual chemicals and mixtures with Alu and LINE-1 methylation. Conclusion: Urinary metals as individual chemicals and mixtures were associated with increased oxidative stress, especially Se.