| Project/Area Number |
20591930
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Showa University |
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Principal Investigator |
SEKIZAWA Akihiko Showa University, 医学部, 准教授 (10245839)
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| Co-Investigator(Kenkyū-buntansha) |
吉村 志帆 昭和大学, 医学部, 普通研究生 (50384441)
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| Co-Investigator(Renkei-kenkyūsha) |
PURWOSUNU Yuditiya University of Indonesia, Faculty of Medicine, Medical Doctor
FARINA Antonio University of Bologna, Faculty of Medicine, Assistant professor
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 妊娠高血圧症候群 / 発症予知 / 母体血中cell-free RNA / 細胞成分由来RNA / 絨毛採取 / 血管増殖因子 / 酸化ストレス / cell-free RNA / 抗血管増殖因子 / cellular RNA / 母体血 / 母体血漿 / 予知 / 胎盤 |
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| Research Abstract |
Increased production of placental anti-angiogenic and anti-oxidative factors are considered to play a crucial role in the pathogenesis of preeclampsia(PE). These placental alterations in women who develop PE in later gestation are thought to begin during the first trimester when extravillous trophoblasts remodel into the endothelial cells of the spiral arteries. We have observed the in vivo alteration of gene expressions in the 1^<st> trimester-trophoblasts from pregnant women who destined to develop PE later. This study prospectively collected tissue samples of villous trophoblasts at the time of fetal karyotype analysis through chorionic villous sampling (CVS), and assessed the mRNA expression of these genes. The results revealed that the expression levels of FLT-1, ENG, VEGF, and TGF-β1 were significantly higher in the CVS tissues from pregnant women who later developed PE whereas the levels of PlGF, HO-1, and superoxide dismutase (SOD) were lower. These findings suggest that the ex
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pression of genes associated with angiogenesis and anti-oxidant stress have crucial roles in the pathogenesis of PE, and that measurement of the expression of these factors in the maternal blood may enable the prediction of the onset of PE.
Fetal/placental RNA circulates in the plasma or cellular compartment of maternal blood and it has enabled the development of several promising approaches for non-invasive evaluation of placental function. Therefore, to prove the possibility of predicting PE by cell-free or cellular RNA in maternal blood, the expression of 7 genes including FLT-1, ENG and VEGF were assessed in the blood of pregnant women between 15 and 20 weeks. We found that this panel of plasma RNA allows an 84% prediction rate for PE with a 5% false positive rate at gestational week 15-20 by means of a discriminant analysis model. The same results were detected in the cellular RNA in maternal blood. Next, to determine whether the combined distribution of a panel of cellular messenger RNA markers at 1^<st> trimester can detect PE long before onset, we assessed cellular RNA levels in the pregnant women between 11 and 14 weeks. As results, higher values than expected were found for ENG, FLT-1, and TGF-β1, and lower values were found for PlGF and placental protein 13. The panel of cellular RNA allows an 72.3% prediction rate for PE with a 5% false positive rate at gestational week 11-14.
These findings indicate that the analyses of cell-free or cellular RNA obtained from pregnant women at early gestation are highly promising methods to evaluate alterations in placental function. Less
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