Effects of maternal smoking on the placental expression of genes related to angiogenesis and apoptosis during the first trimester

PLoS One. 2014 Aug 28;9(8):e106140. doi: 10.1371/journal.pone.0106140. eCollection 2014.

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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Chorionic Villi / drug effects*
  • Chorionic Villi / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Neovascularization, Physiologic*
  • Placenta Growth Factor
  • Pregnancy
  • Pregnancy Proteins / genetics
  • Pregnancy Trimester, First / drug effects
  • Pregnancy Trimester, First / genetics*
  • Smoking / adverse effects*
  • Tumor Suppressor Protein p53 / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Young Adult
  • bcl-2-Associated X Protein / genetics

Substances

  • BAX protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PGF protein, human
  • Pregnancy Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sport and Culture of Japan (No. 26462501), Smoking Research Foundation, and JAOG Ogyaa Donation Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.