title: Effect of maternal tobacco smoke exposure on the placental transcriptome.
abstract: Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious neonatal health problems and chronic lifelong disabilities for the children (e.g., mental retardation, learning problems). To study the effects of tobacco smoke on the placental transcriptome, we performed gene expression profiling on placentas from women exposed to tobacco smoke in pregnancy (N = 12) and from those without significant exposure (N = 64). Gene expression profiles were determined by Illumina HumanRef-8 v2 Expression BeadChips with 18,216 gene probes. Microarray data were normalized by quantile method and filtered for a detection P-value <0.01. Differential gene expression was determined by moderated t-statistic. A linear model was fitted for each gene given a series of arrays using lmFit function. Multiple testing correction was performed using the Benjamini and Hochberg method. Abundant levels of transcripts were found for genes encoding placental hormones (CSH1, CSHL1), pregnancy-specific proteins (PSG3, PSG4, PAPPA), and hemoglobins (HBB, HBG, HBA). Comparative analysis of smokers vs nonsmokers revealed the differential expression of 241 genes (P < 0.05). In smoker cohort, we detected high up-regulation of xenobiotic genes (CYP1A1, CYP1B1, CYB5A, COX412), collagen genes (e.g., COL6A3, COL1A1, COL1A2), coagulation genes (F5, F13A1) as well as thrombosis-related genes (CD36, ADAMTS9, GAS6). In smokers, we identified deregulated genes that show tissue non-specific induction and may be considered as general biomarkers of tobacco smoke exposure. Further, we also found genes specifically deregulated in the exposed placentas. Functional annotation analysis suggested processes and pathways affected by tobacco smoke exposure that may represent molecular mechanisms of smoke-induced placental abnormalities.
authors.affiliation: Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. hana.bruchova@uhkt.cz
authors.forename: H
authors.initials: H
authors.lastname: Bruchova
authors.forename: A
authors.initials: A
authors.lastname: Vasikova
authors.forename: M
authors.initials: M
authors.lastname: Merkerova
authors.forename: A
authors.initials: A
authors.lastname: Milcova
authors.forename: J
authors.initials: J
authors.lastname: Topinka
authors.forename: I
authors.initials: I
authors.lastname: Balascak
authors.forename: A
authors.initials: A
authors.lastname: Pastorkova
authors.forename: R J
authors.initials: RJ
authors.lastname: Sram
authors.forename: R
authors.initials: R
authors.lastname: Brdicka
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010920:Placenta / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012907:Smoking / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger