Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds

Abstract

Environmental exposures in-utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (> 10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (< 1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p< 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean=15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean=29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r= -0.72, p < 0.01) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.

Figure 1

Global DNA methylation index in cord blood serum DNA of 11 newborns exposed in utero to tobacco smoke constituents from maternal smoking, 11 newborns whose mothers were passive smokers and eight newborns whose mothers were nonsmokers. (Box plots).

Figure 2

(A) Linear relationship between the natural log of cotinine in cord blood serum and the global DNA methylation index in 30 newborns with high (11), low (11) and very low (8) cotinine serum levels. (B) Linear relationship between the natural log of PFOA in cord blood serum and the global DNA methylation index in 30 newborns. (C) Linear relationship between the natural log of PFOS in cord blood serum and the global DNA methylation index in 30 newborns.