Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, U Nemocnice 1, Prague 2, Czech Republic.
Placenta. 2011 Oct;32(10):763-70. doi: 10.1016/j.placenta.2011.06.022. Epub 2011 Jul 30.
Maternal smoking has a negative effect on all stages of pregnancy. Tobacco smoke-related defects are well established at the clinical level; however, less is known about molecular mechanisms underlying these pathologic conditions. We thus performed a comprehensive analysis of transcriptome alterations induced by smoking in maternal and fetal cells.
Samples of peripheral blood (PB), placenta (PL), and cord blood (UCB) were obtained from pregnant smokers (n = 20) and gravidas without significant exposure to tobacco smoke (n = 52). Gene expression profiles were assayed by Illumina Expression Beadchip v3 for analysis of 24,526 transcripts. The quantile method was used for normalization. Differentially expressed genes were analyzed in the Limma package and the P-values were corrected for multiple testing. Unsupervised hierarchical clustering was performed using average linkage and Euclidean distance. The enrichment of deregulated genes in biological processes was analyzed in DAVID database.
Comparative analyses defined significant deregulation of 193 genes in PB, 329 genes in PL, and 49 genes in UCB of smokers. The deregulated genes were mainly related to xenobiotic metabolism, oxidative stress, inflammation, immunity, hematopoiesis, and vascularization. Notably, functional annotation of the affected genes identified several deregulated pathways associated with autoimmune diseases in the newborns of smokers.
The study demonstrated maternal smoking causes significant changes in transcriptome of placental and fetal cells that deregulate numerous biological processes important for growth and development of the fetus. An activation of fetal CYP genes showed a limited ability of the placenta to modulate toxic effects of maternal tobacco use.
母亲吸烟对妊娠各阶段都有负面影响。烟草烟雾相关的缺陷在临床水平上已经得到充分证实；然而，对于这些病理状况背后的分子机制知之甚少。因此，我们对吸烟引起的母胎细胞转录组变化进行了全面分析。
从吸烟孕妇（n=20）和未接触大量烟草烟雾的孕妇（n=52）中采集外周血（PB）、胎盘（PL）和脐血（UCB）样本。通过 Illumina Expression Beadchip v3 检测 24526 个转录本的基因表达谱。采用分位数法进行归一化。在 Limma 包中分析差异表达基因，并对 P 值进行多重检验校正。采用平均链接和欧式距离进行无监督层次聚类。在 DAVID 数据库中分析失调基因在生物学过程中的富集情况。
比较分析定义了吸烟孕妇 PB 中 193 个基因、PL 中 329 个基因和 UCB 中 49 个基因的显著失调。失调基因主要与外源性代谢物、氧化应激、炎症、免疫、造血和血管生成有关。值得注意的是，受影响基因的功能注释确定了几个与吸烟者新生儿自身免疫性疾病相关的失调途径。
该研究表明，母亲吸烟会导致胎盘和胎儿细胞的转录组发生显著变化，从而失调许多对胎儿生长发育至关重要的生物学过程。胎儿 CYP 基因的激活表明胎盘对母体烟草使用的毒性作用的调节能力有限。
