Transcriptome alterations in maternal and fetal cells induced by tobacco smoke H. Votavova a, * , 1 , M. Dostalova Merkerova a,1 , K. Fejglova a, 1 , A. Vasikova a , Z. Krejcik a , A. Pastorkova b , N. Tabashidze b , J. Topinka b , M. Veleminsky Jr. c , R.J. Sram b , R. Brdicka a a Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, U Nemocnice 1, 128 20 Prague 2, Czech Republic b Institute of Experimental Medicine, AS CR, 142 20 Prague 4, Czech Republic c Hospital Ceske Budejovice a.s., Ceske Budejovice 370 01, Czech Republic article info Article history: Accepted 27 June 2011 Keywords: Maternal smoking Transcriptome Placenta Cord blood Functional annotation abstract 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 ¼ 20) and gravidas without significant exposure to tobacco smoke (n ¼ 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 clus- tering 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. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Despite a massive widespread edifying campaign against tobacco smoking in pregnancy and its scientifically proven risks for the developing fetus, the awareness is still not sufficient to persuade women to discontinue smoking. Several studies have documented that nearly one-third of pregnant women continue to smoke during pregnancy and the number is even higher among younger gravidas [1]. Exposure to toxic compounds contained in tobacco smoke is dangerous for proper intrauterine fetal growth, causing numerous obstetric and developmental complications. The consequential adverse effects of smoking during pregnancy include spontaneous abortion, placenta previa, placental abruption, preterm birth, stillbirth, fetal growth restriction, low birth weight, and sudden infant death syndrome (SIDS) [2]. Chemical compounds contained in cigarette smoke induce generation of genotoxic and pre-carcinogenic lesions, not only in the cells of primary contact, but also in various secondary tissues. The effects of tobacco smoke exposure on the transcriptomes in the lungs and peripheral blood cells of smokers have been clearly documented [3,4]. Cigarette smoking alters the expression of genes involved in oxidative stress, immune and inflammatory responses, xenobiotic metabolism (particularly cytochromes CYP1A1 and CYP1B1), coagulation and fibrinolysis, oncogenesis, heat-shock * Corresponding author. Tel.: þ420 221977306; fax: þ420 221977371. E-mail addresses: Hana.Bruchova@uhkt.cz (H. Votavova), Michaela.Merkerova@ uhkt.cz (M. Dostalova Merkerova), Kamila.Fejglova@seznam.cz (K. Fejglova), avasikova@seznam.cz (A. Vasikova), Zdenek.Krejcik@uhkt.cz (Z. Krejcik), apastor@ biomed.cas.cz (A. Pastorkova), tabashidze@biomed.cas.cz (N. Tabashidze), jtopinka@biomed.cas.cz (J. Topinka), velem@zsf.jcu.cz (M. Veleminsky), sram@ biomed.cas.cz (R.J. Sram), Radim.Brdicka@uhkt.cz (R. Brdicka). 1 The authors contributed equally to this work. Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.06.022 Placenta 32 (2011) 763e770