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
To analyze the contribution of the Czech population to the Y-chromosome diversity landscape of Europe and to reconstruct past demographic events, we typed 257 males from five locations for 21 UEPs. Moreover, 141 carriers of the three most common haplogroups were typed for 10 microsatellites and coalescent analyses applied. Sixteen Hg's characterized by derived alleles were identified, the most common being R1a-SRY(10831) and P-DYS257*(xR1a). The pool of haplogroups within I-M170 represented the third most common clade. Overall, the degree of population structure was low. The ages for Hg I-M170, P-DYS257*(xR1a), and R1a-SRY(10831) ap peared to be comparable and compatible with their presence during or soon after the LGM. A signal of population growth beginning in the first millennium B.C. was detected. Its similarity among the three most common Hg's indicated that growth was characteristic for a gene pool that already contained all of them. The Czech population appears to be influenced, to a very moderate extent, by genetic inputs from outside Europe in the post-Neolithic and historical times. Population growth postdated the archaeologically documented introduction of Neolithic technology and the estimated central value coincides with a period of repeated changes driven by the development of metal technologies and the associated social and trade organization.
- MeSH
- analýza rozptylu MeSH
- DNA primery MeSH
- genetická variace * MeSH
- haplotypy genetika MeSH
- lidé MeSH
- lidský chromozom Y genetika MeSH
- mikrosatelitní repetice genetika MeSH
- molekulární evoluce * MeSH
- populační dynamika * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- DNA krev MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DR antigeny genetika MeSH
- lidé MeSH
- populační genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Rakousko MeSH
- MeSH
- DNA MeSH
- klinické laboratorní techniky MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- genom lidský MeSH
- lidé MeSH
- lidské chromozomy, pár 14 MeSH
- Check Tag
- lidé MeSH
