Department of Biomedicine, Aarhus University, Denmark; Faculty of Sciences, University of Novi Sad, Serbia.
Department of Biomedicine, Aarhus University, Denmark.
Environ Toxicol Pharmacol. 2018 Jan;57:19-27. doi: 10.1016/j.etap.2017.11.007. Epub 2017 Nov 16.
Prenatal exposure to maternal cigarette smoking increases the risk of intrauterine growth retardation, adverse pregnancy outcomes, and diseases later in life. Exposure can result in postnatal global and gene-specific DNA methylation changes, with the latter well documented for the CYP1A1 and AHRR genes involved in the detoxification of xenobiotic substances. This study assessed the impact of exposure to maternal smoking on first trimester fetal CYP1A1 and AHRR mRNA expression and DNA methylation for CpG-sites displaying maternal smoking during pregnancy-mediated methylation changes at birth. The analyses included first trimester (6-12 weeks) placentas (N=39) and livers (N=43). For AHRR, exposure to maternal smoking was associated with increased DNA methylation in the placentas of female fetuses; mRNA expression, however, was unchanged. While exposure to maternal smoking was not associated with AHRR DNA methylation changes in fetal livers; mRNA expression was increased. For CYP1A1, exposure to maternal smoking was not associated with fetal DNA methylation changes whereas mRNA expression increased in placentas and male fetal livers. These results show that first trimester exposure to maternal smoking is associated with CYP1A1 and AHRR DNA methylation and mRNA expression changes. However, the results also indicate that maternal smoking during pregnancy-mediated postnatal CYP1A1 and AHRR DNA methylation changes are not imprinted during the first trimester.
产前暴露于母体吸烟会增加宫内生长迟缓、不良妊娠结局和生命后期疾病的风险。接触可能导致产后全球和基因特异性 DNA 甲基化改变，后者在 CYP1A1 和 AHRR 基因中得到了很好的证明，这些基因参与了外源物质的解毒。本研究评估了母体吸烟暴露对胎儿 CYP1A1 和 AHRR mRNA 表达和 DNA 甲基化的影响，这些基因在出生时显示了母体吸烟介导的 CpG 位点的甲基化变化。该分析包括第一孕期（6-12 周）胎盘（N=39）和肝脏（N=43）。对于 AHRR，母体吸烟暴露与女性胎儿胎盘 DNA 甲基化增加有关；然而，mRNA 表达不变。虽然母体吸烟暴露与胎儿肝脏中 AHRR 的 DNA 甲基化变化无关，但 mRNA 表达增加。对于 CYP1A1，母体吸烟暴露与胎儿 DNA 甲基化变化无关，而胎盘和男性胎儿肝脏中的 mRNA 表达增加。这些结果表明，第一孕期暴露于母体吸烟与 CYP1A1 和 AHRR 的 DNA 甲基化和 mRNA 表达变化有关。然而，结果也表明，妊娠期间母体吸烟介导的 CYP1A1 和 AHRR DNA 甲基化变化在第一孕期没有被印记。
