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

Epigenetics. 2015;10(11):1054-63. doi: 10.1080/15592294.2015.1105424.


Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero 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 P < 0.001), placenta (Max F P < 0.001), and HUVEC (Max F P = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F P = 0.02), placenta (Max F P = 0.02), and HUVEC (Max F P = 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.

Keywords: DNA methylation; Illumina 450K; arsenic; environmental epigenetics; epigenetics; fetal programming; in utero exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arsenic / toxicity*
  • CpG Islands / drug effects
  • DNA Methylation / drug effects
  • Epigenomics / methods*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Maternal Exposure / adverse effects*
  • Placenta / drug effects*
  • Pregnancy
  • Umbilical Arteries / drug effects*


  • Arsenic