title: Effects of maternal smoking on the placental expression of genes related to angiogenesis and apoptosis during the first trimester.
abstract: OBJECTIVE
  Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women.
  
  
  METHODS
  We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6-8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR.
  
  
  RESULTS
  The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group.
  
  
  CONCLUSIONS
  Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Koide
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Walter
authors.initials: W
authors.lastname: Ventura
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hori
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takenaka
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Maruyama
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Matsuoka
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ichizuka
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sekizawa
mesh_terms: D000328:Adult; D017209:Apoptosis; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D018919:Neovascularization, Physiologic; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics; D011261:Pregnancy Trimester, First / Q000187:drug effects / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1