title: Transcriptome alterations in maternal and fetal cells induced by tobacco smoke.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, U Nemocnice 1, Prague 2, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Votavova
authors.forename: M
authors.initials: M
authors.lastname: Dostalova Merkerova
authors.forename: K
authors.initials: K
authors.lastname: Fejglova
authors.forename: A
authors.initials: A
authors.lastname: Vasikova
authors.forename: Z
authors.initials: Z
authors.lastname: Krejcik
authors.forename: A
authors.initials: A
authors.lastname: Pastorkova
authors.forename: N
authors.initials: N
authors.lastname: Tabashidze
authors.forename: J
authors.initials: J
authors.lastname: Topinka
authors.forename: M
authors.initials: M
authors.lastname: Veleminsky
authors.forename: R J
authors.initials: RJ
authors.lastname: Sram
authors.forename: R
authors.initials: R
authors.lastname: Brdicka
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology*; D055815:Young Adult
chemical_list: D012313:RNA; D003367:Cotinine