Abstract
BackgroundPrenatal exposure to arsenic has been linked to a range of adverse health conditions in later life. Such fetal origins of disease are frequently the result of environmental effects on the epigenome, leading to long-term alterations in gene expression. Several studies have demonstrated effects of prenatal arsenic exposure on DNA methylation; however the impact of arsenic on the generation and decoding of post-translational histone modifications (PTHMs) is less well characterized, and has not been studied in the context of prenatal human exposures.MethodsIn the current study, we examined the effect of exposure to low-to-moderate levels of arsenic in a US birth cohort, on the expression of 138 genes encoding key epigenetic regulators in the fetal portion of the placenta. Our candidate genes included readers, writers and erasers of PTHMs, and chromatin remodelers.ResultsArsenic exposure was associated with the expression of 27 of the 138 epigenetic genes analyzed. When the cohort was stratified by fetal sex, arsenic exposure was associated with the expression of 40 genes in male fetal placenta, and only 3 non-overlapping genes in female fetal placenta. In particular, we identified an inverse relationship between arsenic exposure and expression of the gene encoding the histone methyltransferase, PRDM6 (p < 0.001). Mutation of PRDM6 has been linked to the congenital heart defect, patent ductus arteriosus.ConclusionsOur findings suggest that prenatal arsenic exposure may have sex-specific effects on the fetal epigenome, which could plausibly contribute to its subsequent health impacts.
Highlights
Prenatal exposure to arsenic has been linked to a range of adverse health conditions in later life
In this study, we examined the effect of prenatal exposure to arsenic, at common environmental levels, on the fetal expression of key epigenetic regulators
These results are consistent with our previous work, in which we found that the expression of a candidate set of developmental and stemness genes in the fetal placenta was associated with urinary arsenic (U-As) levels in a sex-specific manner [14]
Summary
Prenatal exposure to arsenic has been linked to a range of adverse health conditions in later life. Such fetal origins of disease are frequently the result of environmental effects on the epigenome, leading to longterm alterations in gene expression. Analyses of data from the NHBCS have revealed associations between prenatal arsenic exposure and measures of fetal and newborn growth [5, 6]; rates of infant infections [7]; immune profiles, inflammatory markers, and leptin levels in cord blood [8,9,10]; and gene expression and DNA methylation in fetal placenta [11,12,13,14,15]. The mechanisms that link arsenic’s molecular effects with its impacts on infant health are still being determined
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