Shin Takenaka

Effects of Maternal Smoking on the Placental Expression of Genes Related to Angiogenesis and Apoptosis during the First Trimester

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.

Vitamin C Induces the Reduction of Oxidative Stress and Paradoxically Stimulates the Apoptotic Gene Expression in Extravillous Trophoblasts Derived From First-Trimester Tissue

Aim: To investigate the effects of vitamin C on the expression of the genes related to apoptosis in extravillous trophoblasts (EVTs) in the first trimester. Methods: Extravillous trophoblasts were cultured under 2% O2 followed by 2% O2 or 8% O2 with or without vitamin C. The level of reactive oxygen species (ROS) in the cultured medium was estimated using electron spin resonance spectroscopy. The expression levels of the genes TP53, BCL2, and BAX were quantified using real-time quantitative polymerase chain reaction. Results: Reactive oxygen species were found to be decreased after adding vitamin C under increasing oxygen concentrations. In addition, the ratio of BAX/BCL2 also increased after adding vitamin C under conditions of 2% O2, while the gene expression level of BCL2 increased after adding vitamin C under increasing oxygen concentrations. In contrast, the gene expression level of TP53 and the ratio of BAX/BCL2 both decreased. Conclusion: We have revealed that vitamin C reduces ROS and may promote the apoptosis of EVTs under conditions of 2% O2 while paradoxically preventing apoptosis under increasing oxygen concentrations.

A three-step evaluation for safer curettage treatment of cesarean scar pregnancy

Dilation and curettage is one of the treatment options for cesarean scar pregnancy, however, it sometimes requires a salvage therapy. Few reports discuss the methods of evaluating cesarean scar pregnancy before therapeutic procedures. We aimed to present a case study in which a three-step approach using a combination of preoperational sonohysterography, hysteroscopy, and laparoscopy was performed to evaluate cesarean scar pregnancy. A 33-year-old, G2P2, Japanese female with a history of two elective cesarean sections was diagnosed with viable cesarean scar pregnancy. We used the three-step approach right after undergoing bilateral uterine artery embolization and confirmed that there was a low possibility of fatal complications and we performed dilation and curettage. These steps could be done safely even if the cesarean scar pregnancy was viable. To perform safer curettage on cesarean scar pregnancy patients, these three steps seem to be useful.

Maternal Smoking History Enhances the Expression of Placental Growth Factor in Invasive Trophoblasts at Early Gestation Despite Cessation of Smoking

Maternal smoking during early pregnancy is associated with a reduced risk for preeclampsia even after smoking cessation during pregnancy. Although the pathophysiology of preeclampsia has not been established, placental growth factor (PlGF) is believed to be a key factor. The aim of this study was to assess the effect of maternal smoking on the PlGF expression in invasive trophoblasts at early gestation. We collected villous tissues from women requesting surgical termination due to non-medical reasons at 7-8 weeks of gestation. The maternal smoking status was evaluated by measuring the serum cotinine level and patients were divided into two groups: active smokers and non-smokers. After separating invasive trophoblasts from villous tissues cultured initially under 2% O2 for 24 hours, the separated invasive trophoblasts were cultured under 2% or 8% O2 for 48 hours. The expression levels of the PlGF gene in villous tissue specimens and in invasive trophoblasts cultured after the conditions were quantified using qRT-PCR. The levels of PlGF protein in the medium were quantified using an ELISA. The gene expression level of PlGF in the villi in the active-smokers was significantly higher than that of the non-smokers. In comparison of the invasive trophoblasts under normoxia and oxygenated conditions, the ratio of PlGF gene expression and protein expression under oxygenation (2% O2+8% O2 / 2% O2+2% O2) in the active-smokers were both significantly higher than in the non-smokers. Maternal smoking history appears to stimulate PlGF expression in invasive trophoblasts under oxygenated conditions. This may be one of several causes leading to the protective effect of maternal smoking on preeclampsia.