Grant-in-Aid for Scientific Research (C)
Obstetrics and gynecology
|Research Institution||Tokyo Women's Medical University|
NAKABAYASHI Masao Tokyo Women's Medical University, Medicine, Professor, 医学部, 教授 (70114585)
HIRANO Ikuko Tokyo Women's Medical University, Medicine, MD, 医学部, 助手 (80256601)
SHIOZAKI Mioko Tokyo Women's Medical University, Medicine, MD, 医学部, 助手 (90226093)
佐倉 まり 東京女子医科大学, 医学部, 助手 (20256613)
|Project Fiscal Year
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
|Keywords||preeclampsia / placenta / urokinase type plasminogen activator (uPA) / plasminogen activator inhibitor 1 (RAI-1) / thrombomodulin / transforming growth factor-beta (TGF-beta) / fetal fibronectin / 妊娠中毒症 / 胎盤 / ウロキナーゼタイププラスミノゲンアクチベータ / PAI-1 / トロンボモジュリン / TGF-β / 胎児性フィブロネクチン / uPA / uPAレセプター|
Object : Impaired invasion of the chorionic villi to the basement decidual layer is a possible pathogenesis of preeclampsia. In the process of placentation, the involvement of coagulation and fibrinolytic systems and cytokines in the placenta is suggested. The object of this study is to elucidate the role of coagulation and fibrinolytic systems in the process of placentation in normal and preeclamptic patients.
Methods : We analyzed the fibrinolytic factors - urokinase type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and thrombomodulin (TM) in normal placentae of the 1st, 2nd and 3rd trimester. These results were compared to those of preeclamptic patients.
In addition, transforming growth factor-beta (TGF-beta), which is released by platelet aggregation, was added to cultures of isolated placental cells collected in early pregnancy to examine the effects of TGF-beta on the productions of fetal fibronectin (FFN) and PAI-1.
Results : 1. It wa
s revealed immunohistochemical by that the localization of uPA and uPAR was recognized in the cytotrophoblastic cells and extravillous trophoblastic cells of the 1st and 2nd trimester placenta.
2. The levels of uPA and uPAR in the 3rd trimester placenta were lower than those in the 1st and 2nd trimester placenta, and there were no differences between those in normal and preeclamptic patients.
3. The levels of PAI-1 in decidual extracts of preeclampsia were significantly higher than those of normal.
4. The levels of TM in chorionic extracts of preeclampsia were significantly lower than those of normal.
5. TGF-beta significantly increased both PAI-1 production in decidual cells and FFN production in chorionic cells in culture in a dose-dependent manner.
Conclusions : 1. These results suggest that expression of uPA and uPAR on trophoblasts may play an important role in the regulation mechanisms of the invasion and implantation of the placenta.
2. It was suggested that the promotion of platelet aggregation and a local increase in TGF-beta in the placenta may contribute to the occurrence of preeclampsia.
3. It was suggested that placental circulation in preeclampsia was in a hypercoagulable and hypofibronolytic state. Less