Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic <i>in utero</i>

<div><p>Mercury and arsenic are known developmental toxicants. Prenatal exposures are associated with adverse childhood health outcomes that could be in part mediated by epigenetic alterations that may also contribute to altered immune profiles. In this study, we examined the association between prenatal mercury exposure on both DNA methylation and white blood cell composition of cord blood, and evaluated the interaction with prenatal arsenic exposure. A total of 138 mother-infant pairs with postpartum maternal toenail mercury, prenatal urinary arsenic concentrations, and newborn cord blood were assessed using the Illumina Infinium Methylation450 array. White blood cell composition was inferred from DNA methylation measurements. A doubling in toenail mercury concentration was associated with a 2.5% decrease (95% CI: 5.0%, 1.0%) in the estimated monocyte proportion. An increase of 3.5% (95% CI: 1.0, 7.0) in B-cell proportion was observed for females only. Among the top 100 CpGs associated with toenail mercury levels (ranked on <i>P-value</i>), there was a significant enrichment of loci located in North shore regions of CpG islands (<i>P</i> = 0.049), and the majority of these loci were hypermethylated (85%). Among the top 100 CpGs for the interaction between arsenic and mercury, there was a greater than expected proportion of loci located in CpG islands (<i>P</i> = 0.045) and in South shore regions (<i>P</i> = 0.009) and all of these loci were hypermethylated. This work supports the hypothesis that mercury may be contributing to epigenetic variability and immune cell proportion changes, and suggests that <i>in utero</i> exposure to mercury and arsenic, even at low levels, may interact to impact the epigenome.</p></div

In <i>utero</i> arsenic exposure and epigenome-wide associations in placenta, umbilical artery, and human umbilical vein endothelial cells

<p>Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming <i>in utero</i>. In the present study, we evaluate the epigenome-wide association of arsenic exposure <i>in utero</i> and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and 4 CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F <i>P</i> < 0.001), placenta (Max F <i>P</i> < 0.001), and HUVEC (Max F <i>P</i> = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F <i>P</i> = 0.02), placenta (Max F <i>P</i> = 0.02), and HUVEC (Max F <i>P</i> = 0.02). Our results show that prenatal arsenic exposure can alter DNA methylation in artery and placenta but not in HUVEC. Further studies are needed to determine if these alterations in DNA methylation mediate the effect of prenatal arsenic exposure and health outcomes later in life.</p