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Epigenetics. 2014 Feb;9(2):212-21. doi: 10.4161/epi.26798. Epub 2013 Oct 28.

Cadmium exposure and the epigenome: Exposure-associated patterns of DNA methylation in leukocytes from mother-baby pairs.

Author information

1
Department of Environmental Sciences and Engineering; Gillings School of Global Public Health; University of North Carolina; Chapel Hill, NC USA.
2
Curriculum in Toxicology; School of Medicine; University of North Carolina; Chapel Hill, NC USA.
3
Center for Bioinformatics; University of North Carolina; Chapel Hill, NC USA.
4
Department of Biostatistics; Gillings School of Global Public Health; University of North Carolina; Chapel Hill, NC USA.
5
Department of Epidemiology; Gillings School of Global Public Health; University of North Carolina; Chapel Hill, NC USA.
6
Department of Obstetrics and Gynecology; Duke University; Durham, NC USA.
7
Center for Human Genetics; Duke University Medical Center; Durham, NC USA.
8
School of Natural Resources and Environment; Department of Pediatrics; University of Michigan; Ann Arbor, MI USA.
9
Department of Environmental Sciences and Engineering; Gillings School of Global Public Health; University of North Carolina; Chapel Hill, NC USA; Curriculum in Toxicology; School of Medicine; University of North Carolina; Chapel Hill, NC USA.

Abstract

Cadmium (Cd) is prevalent in the environment yet understudied as a developmental toxicant. Cd partially crosses the placental barrier from mother to fetus and is linked to detrimental effects in newborns. Here we examine the relationship between levels of Cd during pregnancy and 5-methylcytosine (5mC) levels in leukocyte DNA collected from 17 mother-newborn pairs. The methylation of cytosines is an epigenetic mechanism known to impact transcriptional signaling and influence health endpoints. A methylated cytosine-guanine (CpG) island recovery assay was used to assess over 4.6 million sites spanning 16,421 CpG islands. Exposure to Cd was classified for each mother-newborn pair according to maternal blood levels and compared with levels of cotinine. Subsets of genes were identified that showed altered DNA methylation levels in their promoter regions in fetal DNA associated with levels of Cd (n = 61), cotinine (n = 366), or both (n = 30). Likewise, in maternal DNA, differentially methylated genes were identified that were associated with Cd (n = 92) or cotinine (n = 134) levels. While the gene sets were largely distinct between maternal and fetal DNA, functional similarities at the biological pathway level were identified including an enrichment of genes that encode for proteins that control transcriptional regulation and apoptosis. Furthermore, conserved DNA motifs with sequence similarity to specific transcription factor binding sites were identified within the CpG islands of the gene sets. This study provides evidence for distinct patterns of DNA methylation or "footprints" in fetal and maternal DNA associated with exposure to Cd.

KEYWORDS:

cadmium; cigarette smoke; cord blood; epigenetics; heavy metal; maternal blood; methylation; pregnancy

PMID:
24169490
PMCID:
PMC3962531
DOI:
10.4161/epi.26798
[Indexed for MEDLINE]
Free PMC Article

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