Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.
BACKGROUND
An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown.


OBJECTIVE
The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh.


METHODS
Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA.


RESULTS
In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05).


CONCLUSIONS
These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings and to examine the persistence of DNA methylation marks over time.
Division of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America.
J Richard
JR
Pilsner
Megan N
MN
Hall
Xinhua
X
Liu
Vesna
V
Ilievski
Vesna
V
Slavkovich
Diane
D
Levy
Pam
P
Factor-Litvak
Mahammad
M
Yunus
Mahfuzar
M
Rahman
Joseph H
JH
Graziano
Mary V
MV
Gamble
D000328:Adult; D020087:Alu Elements; D001151:Arsenic / Q000633:toxicity*; D001773:Blood Cells / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D012737:Sex Factors; D055815:Young Adult
D001151:Arsenic