Dataset Information

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes.

ABSTRACT:

Background

Arsenic is an epigenetic toxicant and could influence fetal developmental programming.

Objectives

We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.

Methods

Drinking-water and urine samples were collected when women were at ? 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.

Results

Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 ?g/L (range: < 1-230 ?g/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.

Conclusions

Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.

SUBMITTER: Kile ML

PROVIDER: S-EPMC3404653 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes.

Kile Molly L ML Baccarelli Andrea A Hoffman Elaine E Tarantini Letizia L Quamruzzaman Quazi Q Rahman Mahmuder M Mahiuddin Golam G Mostofa Golam G Hsueh Yu-Mei YM Wright Robert O RO Christiani David C DC

Environmental health perspectives 20120330 7

<h4>Background</h4>Arsenic is an epigenetic toxicant and could influence fetal developmental programming.<h4>Objectives</h4>We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.<h4>Methods</h4>Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and ...[more]

PMID: 22466225

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Project description:Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

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Dataset Information

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes.

Background

Objectives

Methods

Results

Conclusions

Publications

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes.

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