Abstract
Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9–4.9 years) and mid-childhood (n = 291; 6.7–10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.
Highlights
Mercury (Hg) is a ubiquitous worldwide environmental contaminant that can persist in the environment and bioaccumulates as methylmercury (MeHg) in the food chain
To evaluate the functional relevance of methylation changes, we examined whether DNA methylation of the Paraoxonase 1 gene (PON1) Differentially Methylated Regions (DMRs) and differentially methylated single CpGs were correlated with gene expression in cord blood from an independent birth cohort (Biomarkers of Exposure to Arsenic; N = 38)[22]
We showed that higher DNA methylation levels of the PON1 region are associated with lower cognitive test scores in early childhood for both sexes
Summary
Mercury (Hg) is a ubiquitous worldwide environmental contaminant that can persist in the environment and bioaccumulates as methylmercury (MeHg) in the food chain. Several studies have characterized DNA methylation changes in cord blood relative to prenatal environmental exposures, very few studies have evaluated the persistence of these changes into childhood[13]. Three epigenome-wide association studies have been conducted identifying unique genomic regions as well as individual CpG methylation disruption in cord blood[15, 16] and placenta[17] of newborns prenatally exposed to mercury. These studies were limited in sample size (ranging from 41 to 141 samples) and did not evaluate whether the observed epigenetic alterations were persistent, sex-specific or related to cognitive performance in childhood. It is crucial to evaluate sex-specific epigenetic alterations in response to environmental conditions
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