Placental mitochondrial DNA and CYP1A1 gene methylation as molecular signatures for tobacco smoke exposure in pregnant women and the relevance for birth weight

摘要: Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations the utero-placental exchange. Epigenetics and mitochondrial function fetal tissues might be molecular signatures responsive to utero tobacco smoke exposure. In framework ENVIRONAGE cohort, we investigated effect self-reported exposure on relation with placental tissue markers such as, (1) relative DNA (mtDNA) content as determined by real-time quantitative PCR, (2) methylation specific loci of mtDNA (D-loop MT-RNR1), (3) biotransformation gene CYP1A1 (the last two bisulfite-pyrosequencing). The total pregnant mother sample included 255 non-smokers, 65 former-smokers who had quit before pregnancy, 62 smokers continued pregnancy. Smokers delivered newborns a average 208 g lower [95% confidence interval (CI) −318 −99, p = 0.0002] than mothers did not smoker group, was (−21.6%, 95% CI −35.4 −4.9%, p = 0.01) non-smoker group; whereas, absolute levels of MT-RNR1 were higher (+0.62%, 0.21 1.02%, p = 0.003). Lower CpG-specific (−4.57%, −7.15 −1.98%, p < 0.0001) were observed compared non-smokers. Nevertheless, no mediation nor any other signature for association between weight. content, specific mtDNA, may serve gestational