OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
- MeSH
- dospělí MeSH
- fetální krev metabolismus MeSH
- kohortové studie MeSH
- kotinin krev MeSH
- kouření škodlivé účinky krev genetika metabolismus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- placenta metabolismus patologie MeSH
- plod patologie MeSH
- RNA chemie genetika MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- těhotenství MeSH
- transkriptom fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- ATP-synthetasa (komplexy) genetika nedostatek MeSH
- dítě MeSH
- elektroforéza metody využití MeSH
- lidé MeSH
- mitochondriální nemoci diagnóza MeSH
- western blotting metody využití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- kongresy MeSH