Prenatal Exposure to Mercury: Associations with Global DNA Methylation and Hydroxymethylation in Cord Blood and in Childhood

BACKGROUND: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. OBJECTIVES: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood. METHODS: Within Project Viva, a U.S. prebirth cohort, we examined associations of maternal second trimester red blood cell mercury (RBC-Hg) concentrations with global 5-hydroxymethylcytosine ([Formula: see text]) and 5-methylcytosine ([Formula: see text]) DNA content in blood collected at birth ([Formula: see text]), early childhood ([Formula: see text]; 2.9 to 4.9 y), and midchildhood ([Formula: see text]; 6.7 to 10.5 y). RESULTS: Median prenatal RBC-Hg concentration was [Formula: see text] [[Formula: see text]]. At birth, median cord blood [Formula: see text] , [Formula: see text] , and their ratio were 4.95%, 0.22%, and 24.37, respectively. The mean adjusted difference [95% confidence interval (CI)] of blood [Formula: see text] for a doubling in prenatal RBC-Hg concentration was [Formula: see text] ([Formula: see text] , 0.002), [Formula: see text] ([Formula: see text] , [Formula: see text]), and 0.005% ([Formula: see text] , 0.018) at birth, early, and midchildhood, respectively. The corresponding relative adjusted change in the genomic ratio of [Formula: see text] to [Formula: see text] for a doubling in prenatal RBC-Hg concentration was 4.70% (0.04, 9.58), 22.42% (7.73, 39.11), and 0.73% ([Formula: see text] , 5.88) at birth, early, and midchildhood, respectively. No associations were present between prenatal maternal RBC-Hg and [Formula: see text] at any time point. CONCLUSIONS: Prenatal mercury exposure was associated with lower [Formula: see text] genomic content and a corresponding increase in the ratio of [Formula: see text] to [Formula: see text] in cord blood. This association was persistent in early but not midchildhood blood. Our results demonstrate the potential malleability of epigenetic modifications associated with mercury exposure in utero. https://doi.org/10.1289/EHP1467