Placental mitochondrial DNA and CYP1A1 gene methylation as molecular signatures for tobacco smoke exposure in pregnant women and the relevance for birth weight. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Janssen, Bram; Gyselaers, Wilfried; Byun, Hyang-Min; Roels, Harry; Cuypers, Ann; Baccarelli, Andrea; Nawrot, Tim
• Is Part Of: Journal of translational medicine. Volume 15:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Birth weight -- CYP1A1 -- Epigenetics -- DNA methylation -- Mitochondrial DNA content -- Mitochondrial DNA methylation -- Placental tissue -- Tobacco smoke; Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-016-1113-4
• Languages: English
• ISSNs: 1479-5876

Abstract

Abstract Background Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations in theutero -placental exchange. Epigenetics and mitochondrial function in fetal tissues might be molecular signatures responsive to in utero tobacco smoke exposure. Methods In the framework of the ENVIRON AGE birth cohort, we investigated the effect of self-reported tobacco smoke exposure during pregnancy on birth weight and the relation with placental tissue markers such as, (1) relative mitochondrial DNA (mtDNA) content as determined by real-time quantitative PCR, (2) DNA methylation of specific loci of mtDNA (D-loop andMT-RNR1 ), and (3) DNA methylation of the biotransformation geneCYP1A1 (the last two determined by bisulfite-pyrosequencing). The total pregnant mother sample included 255 non-smokers, 65 former-smokers who had quit smoking before pregnancy, and 62 smokers who continued smoking during pregnancy. Results Smokers delivered newborns with a birth weight on average 208 g lower [95% confidence interval (CI) −318 to −99, p = 0.0002] than mothers who did not smoke during pregnancy. In the smoker group, the relative mtDNA content was lower (−21.6%, 95% CI −35.4 to −4.9%, p = 0.01) than in the non-smoker group; whereas, absolute mtDNA methylation levels of MT-RNR1 were higher (+0.62%, 95% CI 0.21 to 1.02%, p = 0.003). Lower CpG-specific methylation ofCYP1A1 in placental tissue (−4.57%, 95% CI −7.15 to −1.98%, p < 0.0001) were observed in smokers compared with non-smokers. Nevertheless, no mediation ofCYP1A1 methylation nor any other investigated molecular signature was observed for the association between tobacco smoke exposure and birth weight. Conclusions mtDNA content, methylation of specific loci of mtDNA, andCYP1A1 methylation in placental tissue may serve as molecular signatures for the association between gestational tobacco smoke exposure and low birth weight.