Akihiro Kawashima

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.

Increased Levels of Cell-Free Human Placental Lactogen mRNA at 28-32 Gestational Weeks in Plasma of Pregnant Women With Placenta Previa and Invasive Placenta:

We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P < .01 and P < .05, respectively. We found a sensitivity of 100% and a specificity of 61.5% for the prediction of invasive placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation.

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.

Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration

The discovery of circulating tumour DNA molecules created a paradigm shift in tumour biomarkers as predictors of recurrence. Non-invasive prenatal testing (NIPT) to detect circulating cell-free foetal DNA in maternal plasma is increasingly recognised as a valuable substitute to perceive foetal copy number variation (CNV). This study aimed to determine whether the copy number detection in plasma samples using NIPT platform could be used as a prognostic biomarker in patients with gynaecological cancer. We conducted a prospective study using samples containing preoperative plasma from 100 women with gynaecological cancers. Samples were randomly rearranged and blindly sequenced using a low-coverage whole-genome sequencing plasma DNA, NIPT platform. The NIPT pipeline identified copy number alterations (CNAs) were counted in plasma as a gain or loss if they exceeded 10 Mb from the expected diploid coverage. Progression-free survival (PFS) and overall survival (OS) were analysed according to the presence of CNA in plasma using Kaplan–Meier analyses. The NIPT pipeline detected 19/100 cases of all gynaecological cancers, including 6/36 ovarian cancers, 3/11 cervical cancers, and 10/53 endometrial cancers. Patients with CNA in plasma had a significantly poorer prognosis in all stages concerning PFS and OS. Therefore, low-coverage sequencing NIPT platform could serve as a predictive marker of patient outcome.

Publisher Correction: Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration

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Can umbilical artery Doppler findings at 36 weeks' gestation predict maternal hypertension at later gestation?

Abstract Objectives: To clarify whether ultrasonographic evaluations of fetoplacental underperfusion using umbilical artery (UmA) Doppler indices at 36 weeks’ gestation can predict maternal hypertension at later gestation. Methods: Normotensive pregnant women who underwent an ultrasound scan at 36 weeks’ gestation and delivered singleton infants at term between 2012 and 2013 were prospectively enrolled. UmA Doppler and maternal blood pressure results at 36 weeks’ gestation in cases with pregnancy-induced hypertension (PIH) at later gestation were compared with a control group. Results: Thirty-nine and 775 cases were classified into the PIH and control group, respectively. The UmA pulsatility index (PI) and maternal systolic blood pressure (SBP) at 36 weeks’ gestation were higher in the PIH group than in control group (UmA-PI: 0.88 vs. 0.80, p = 0.002; SBP: 126 mmHg vs. 112 mmHg, p < 0.001). The area under the ROC curve for the prediction of PIH by combining the UmA-PI and SBP was 0.867 (95% confidence interval (CI): 0.781, 0.954). The detection rate for PIH was 64.0% with a 10% false-positive rate. Conclusions: An increased UmA-PI at 36 weeks’ gestation is associated with the occurrence of PIH at later gestation. This result may indicate the possibility to detect fetoplacental underperfusion ultrasonically.

Intra-aortic balloon occlusion without fluoroscopy for life-threating post-partum hemorrhage

Abstract The use of intra-aortic balloon occlusion (IABO) could be effective in achieving the quick control of bleeding in emergency settings and in supporting the provision of safe radical treatment through resuscitative endovascular balloon occlusion of the aorta (REBOA). We herein report our experience of a patient with life-threatening postpartum hemorrhage after cesarean section who was successfully treated by hysterectomy with IABO without fluoroscopy. We believe that this procedure is very useful and safe, and that it should be considered as one of methods for controlling bleeding in patients with life-threatening postpartum hemorrhage.

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.

Can measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody levels be used to screen for cytomegalovirus infection in embryos and fetuses?

Aims:  Our study aims to estimate whether measurement of maternal anti‐cytomegalovirus immunoglobulin‐M antibody (CMV‐IgM) levels are useful as a screening method for achieving early detection of congenital CMV infection.