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.

425: Maternal tobacco use modestly alters correlated epigenome wide placental DNA methylation and gene expression

“…Thus, 36 matched subjects were analyzed with minimized potential for selection bias. As anticipated, 8,12,[20][21][22][23][24][25][26][27][28] we did observe a significant decrease in infant birth weight among smokers (3,059 g ± 107 versus 3,460 g ± 93, p = 0.008; Table 1). The remainder of the clinical outcome variables was not significantly different among cases and controls (Table 1), and subjects were excluded by virtue of significant maternal or fetal comorbidities (see Methods).…”

“…22 Similarly, global DNA methylation of newborn cord blood is reported to have an inverse relationship with cord blood cotinine levels, being lowest in newborns with the highest serum cotinine levels. 23 At a single gene level, we have previously reported an increase in expression of the Phase I enzyme CYP1A1 in placental tissue from smoking mothers compared with nonsmoking ones. 13 Interrogation of the mechanisms underlying this increased transcription with extensive bisulfite sequencing analysis of 59 CpG sites within the CYP1A1 proximal promoter showed that maternal smoking is associated with a decrease in CpG site-specific methylation specifically surrounding the xenobiotic response element (XRE) promoter element(s), which is significantly correlated with the CYP1A1 gene expression regardless of smoking behavior.…”

In UteroExposure to Second-Hand Smoke Aggravates the Response to Ovalbumin in Adult Mice

“…In another study, Murphy and colleagues (33) reported in utero cigarette smoke-related increases in DNA methylation of insulin-like growth factor 2, which is more pronounced in the male offspring than the females. Epigenetic alterations induced by in utero smoke exposures have been revealed (34,35), with the potential for these alterations to persist into adulthood and modulate adult responses (36,37). We are currently investigating the epigenetic changes associated with SHS exposure in utero to gain more insights into adult disease susceptibility.…”

Epigenetic mechanisms in physiologic and pathologic pregnancies

“…GuerreroPreston és munkacsoportja igazolta, hogy a dohányfüst, illetve a rozsdamentes borításokban található úgyneve-zett perfl uoroalkil vegyületek szignifi kánsan csökkentik a köldökzsinórvér sejtjeinek globális DNS-metilációs szintjét. Ez a köldökzsinórvér egészére gyakorolt markáns epigenetikai hatás erőteljesen befolyásolhatja a magzati oxigenizációt és energiaellátást egyaránt [75]. További vizsgálatok a köldökzsinórvérsejtek IGF-2 gén-jének (insuline-like growth factor 2) metilációs módosu-lását igazolták, amelyet -lévén az anyagcsere egyik fő reguláló génjéről szó -a dohányos várandós nők magzatainak méhen belüli növekedési visszamaradásával hoztak összefüggésbe [76].…”