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PATHOGENESIS OF INTRAUTERINE GROWTHRETARDATION

Research Project

Project/Area Number 04454426
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionTOKYO WOMEN'S MEDICAL COLLEGE

Principal Investigator

TAKEDA Yoshihiko  TOKYO WOMEN'S MED.COLL., PROFESSOR AND CHAIRMAN, 医学部, 教授 (00033069)

Co-Investigator(Kenkyū-buntansha) MORI Akira  TOKYO WOMEN'S MED.COLL., 医学部, 助手 (60219996)
TAKAGI Koichiro  TOKYO WOMEN'S MED.COLL., 医学部, 講師 (90154749)
IWASHITA Mitsutoshi  TOKYO WOMEN'S MED.COLL., 医学部, 助教授 (30124936)
NAKABAYASHI Masao  TOKYO WOMEN'S MED.COLL., 医学部, 教授 (70114585)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsENDOTHELIN / HYPOXIA / PLACENTA / VESSEL PULSE WAVEFORM / HEART FUNCTION / INSULIN-LIKE GROWTHFACTOR / INSULIN-LIKE GROWTHFACTOR BINDING PROTEIN / 低酸素症 / IGF-I, / IGFBP / 血流計測 / Flow Index / 低用量アスピリン / IUGR / 妊娠中毒症 / 脱落膜細胞 / 胎盤絨毛 / IGF-I / IGF結合蛋白 / トロンボモジュリン / ダブルビームドプラー
Research Abstract

1. Insulin-like growth factor-I and its binding proteins (IGFBPs) regulate placental transport function. Expression of IGFBPs translocate from syncytiotrophoblast to cytotrophoblast at early stage of gestation corresponding to differentiation of placental function. Only IGFBP-2 mRNA was expressed predominantly in rat placenta throughout gestation.
2. All four IGFBPs including IGFBP-1, -2, -3, and -4 were identified in fetal circulation throughout pregnancy by Western ligand blot. In contrast to maternal circulation, there was no protease activity in fetal circulation. However, levels of these IGFBPs varied corresponding to fetal growth such as IUGR,giant and preterm infants. Especially, levels of IGFBP-2 were extremely increased in infants with IUGR.Since IGFBP-2 regulates IGF-II rather than IGF-I,this result indicates that physiological significance of IGF-II in fetal growth should be reevaluated.
3. We have demonstrated that fetal acidosis due to hypoxia is correlated with endothelin-1 … More (ET-1) elevation in the fetal circulation. Furthermore, ET-1 gene expression in the rat placenta was augmented two-fold in response to chronic hypoxic stress to the fetus by unilateral ligation of the uterine artery. In an assessment of the fetal systemic circulation, it was possible to record fetal central venous pressure pulse waveforms (CVPW) noninvasively by newly developed measurement of pulsatile changes in vessel diameter. On the CVPW,four waves which were corresponding to right atrial contraction, right ventricular contraction, opening and closure of tricuspid valve were identified from correlation of the fetal electrocardiogram. The newly noninvasive analysis in the degree of right cardiac afterload and cardiac dysfunction was established.
From these results, Pathogenesis of IUGR is pathophysiologically originated from reduced nutritional transfer due to impaired placental exchange in which maladaptation of trophoblast implantation resulted in placental malfunction. Furthermore, it has been elucidated that IGF-I and IGFBPs regulated by interaction between chorion and decidua control placental transport function and that growth and maturation of fetus is regulated by fetal own IGFBPs. On the other hand, ET-1, expressed in the chorionic villi, might be involved in the blood shift from the placenta to the fetal systemic circulation upon fetal hypoxia. The response in the fetal systemic circulation that occur in association with fetal compromise was associated with right cardiac afterload and influenced by the CVPW.The newly developed noninvasive measurement of vessel diameter changes makes it possible to apply for clinical evaluation. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] 岩下光利、三室卓久、中山摂子、武田佳彦、坂元正一: "Insulin-like grouth factor-1(IGF-1)の胎児発育における生理学的意義" 産婦人科の世界. vol44. 145-151 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大平篤、岩下光利、武田佳彦、坂元正一: "Epidermal growth factorのマウス胎仔成熟及び胎盤発育における生理学的意義-抗体中和実験による検討" 日本産科婦人科雑誌. vol44. 275-281 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Iwashita.,M.Kobayashi.,A.Matsuo.,S.Nakayama.,T.Mimuro.,Y.takeda.,S.Sakamoto: "Feto-maternal interaction of IGF-I and its binding proteins in fetal growth." Early Human Development. vol29. 187-191 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 中林正雄、河西洋、武田佳彦: "臍帯径の胎児発育" 産婦人科の実際. vol41. 1811-1813 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岩下光利、坂元正一、中山摂子、三室卓久、安達知子、武田佳彦、安井修司、永井厚志: "IGF-Iとその結合蛋白の胎仔発育および肺成熟にあたえる影響" 日本界面医学学会雑誌. vol23. 69-71 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦、高木耕一郎: "ハイリスク妊娠・分娩と妊産婦死亡 予防・対策" 産婦人科の実際. vol41. 2061-2064 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森晃、武田佳彦: "胎児血管径の実時間変位計測法の開発に関する研究" 日本産科産婦人科会誌. vol44. 1543-1550 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 高木耕一郎、中林正雄、武田佳彦: "未熟児帝切手技の一考案-En Caule Cesarean Section" 関東連合地方部会会誌. vol30 no.1. 171 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岩下光利、武田佳彦: "加齢と性機能 妊娠、産褥期の性機能" 産科と婦人科. vol60 no.6. 811-817 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 中林正雄、原田誠、武田佳彦: "病態と血液浄化療法 産科疾患と血液浄化療法" medicina. vol30 no.5. 922-925 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦: "胎児仮死の病態生理 胎児・新生児仮死の病態" NEW MOOK産婦人科. vol5. 1-5 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森晃、Brian Tndinger、森蘭子、武田佳彦: "胎児血圧の計測" 臨床婦人科産科. vol48 no.3. 312-313 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森晃、Brian Tndinger、森蘭子、武田佳彦: "胎児診断-胎児血圧と脳循環測定法" 周産期医学. vol.48 no.11. 1493-1497 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 中林正雄、原誠、中山摂子、武田佳彦: "妊娠分娩時の脳循環" 周産期医学. vol.24 no.11. 1559-1562 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦、横尾郁子、佐藤孝道、高木耕一郎: "妊産婦と薬物" 日本医師会雑誌. vol.120 no.10. 1425-1431 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岩下光利、武田佳彦: "IGF-Iと胎児発育" 医学のあゆみ. vol.171 no.7. 611-614 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦: "パネルディスカッション「胎児・新生児中枢神経障害の診断・管理・予後判定」 まとめ" 日本新生児学会雑誌. vol.30 no.1. 60-61 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦、岩下光、工藤美樹: "ラット胎仔肝よりのIGFBD-1分泌に及ぼすアミノ酸の影響" 産婦人科治療. vol.68 no.4. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田佳彦: "周産期医療の理論と実戦" ペリネイタル・ケア, 60 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 岩下光利、武田佳彦: "生殖内分泌の最近の進歩 IGFと生殖内分泌" ホルモンと臨床 vol.41, 227-232 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森晃、岩下光利、高木耕一郎、中林正雄、武田佳彦、坂元正一: "血管径拍動波形と血流速度波形から胎児血流量を指標した循環動態の定性分析" 日本産科非人家学会会誌 vol.44, 210 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 工藤美樹、岩下光利、武田佳彦: "図説明産婦人科VIEW-9 胎児発育・成熟とその異常" 胎児発育異常と成長因子(IGF), 104-115 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 中林正雄、安達知子、武田佳彦: "NEW MOOK 産婦人科5 胎児・新生児仮死" 重症妊娠中毒症, 78-85 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Hashiguchi, K.Takagi, Wen-Rong He, K.Ando, Y.Takeda: "Effect of Edothelin-1 on luteal function of pregnancy rat" Folia Endocrinol Jpn. vol.69, No.4. 380 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wen-Rong He, S.Nakayama, K.Takagi, M.Nakabayashi, Y.Takeda: "A case with postpartum HELLP syndrome-is edothelin involved in HELLP syndrome?" J.Japan Society for the Study of Toxemia of Pregnancy. vol.1. 113-114 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Iwashita, M.Kobayashi, A.Matsuo, S.Nakayama, T.Mimuro, Y.Takeda, S.Sakamoto: "Feto-maternal interaction of IGF-1 and its binding proteins in fetal growth" Early Human Development. vol.29. 187-191 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Mori, Y.Takeda: "Development of method for measurement of pulsatile change in arterial diameter in the fetus" Acta Obstet Gynecol Jpn. vol.12. 1543-1550 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Mori, R.Mori, Y.Takeda: "Physiological characteristics of inferior vena cava pulse waveform during foetal development" Physiological measurement. vol.15. 481-488 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森晃 Brian Truclinger 森蘭子 武田佳彦: "胎児診断-胎児血圧と脳循環測定法" 周産期医学. vol.24 no.11. 1493-1497 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 中林正雄.原誠 中山摂子.武田佳彦: "妊娠分娩時の脳循環" 周産期医学. vol.24 no.11. 1559-1562 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田佳彦,横尾郁子 佐藤孝道 高木耕一郎: "妊産婦と薬物" 日本医師会雑誌. vol.112 no.10. 1425-1431 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 岩下光利 武田佳彦: "IGF-Iと胎児発育" 医学のあゆみ. vol.171 no.7. 611-614 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田佳彦: "パネルディスカッション「胎児・新生児中枢神経障害の診断,管理,予後判定」まとめ" 日本新生児学会雑誌. vol.30 no.1. 60-61 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田佳彦 岩下光利 工藤美樹: "ラット胎仔肝よりのIGFBP-1分泌に及ぼすアミノ酸の影響" 産婦人科治療. vol.68 no.4. (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 工藤美樹 岩下光利 武田佳彦: "図説産婦人科VIEW-9 胎児発育・成熟とその異常" 胎児発育異常と成長因子(IGF), 104-115 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 中林正雄 安達知子 武田佳彦: "NEW MOOK産婦人科5 胎児・新生児・仮死" 重症妊娠中毒症, 78-85 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森晃、武田佳彦: "胎児血管径の実時間変位計測法の開発に関する研究" 日本産科婦人科学会誌. 44. 1543-1550 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高木耕一郎、中林正雄、武田佳彦: "未熟児帝切手技の一考案-EnCaule Cesarean Section" 関東連合地方部会会誌. 30〜1. 171 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岩下光利、武田佳彦: "加齢と性機能 妊娠、産褥期の性機能" 産科と婦人科. 60〜6. 811-817 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中林正雄、原田誠、武田佳彦: "病態と血流浄化療法 産科疾患と血液浄化療法" medicina. 30〜5. 922-925 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田佳彦: "胎児仮死の病態生理、胎児、新生児、仮死の病態" NEW MOOK 産婦人科. 5. 1-5 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晃Brian Trudinger 森蘭子、武田: "胎児血圧の計測" 臨床婦人科産科. 48〜3. 312-313 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岩下光利、武田佳彦: "ホルモンと臨床 vol41" 生殖内分泌の最近の進歩 IGFと生殖内分泌, 227〜232 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晃、岩下、高木、中林、武田、坂元: "日本産科婦人科学会誌 vol44" 血管径拍動波形と血流速度波形から胎児血流量を指標した循環動態の定性分析, 210 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岩下 光利、三室 卓久、中山 摂子、武田 佳彦、坂元 正一: "Insulin-like growth factor-I(IGF-I)の胎児発育における生理学的意義" 産婦人科の世界. 第44. 145-151 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大平 篤、岩下 光利、武田 佳彦、坂元 正一: "Epidermas growth factorのマウス胎仔成熟及び胎盤発育における生理的意義-抗体中和実験による検討-" 日本産科婦人科雑誌. 第44. 275-281 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Iwashita,M.Kobayashi,A.Matsuo,S.Nakayama,T.Mimuro,Y.Takeda S.Sakamoto: "Feto-maternal interaction of IGF-I and its binding proteins in fetal growth" Early Human Development.29(1992)187-191 Elsevier Scientific Publishers Ireland Ltd.29. 187-191 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 中林 正雄 河西 洋 武田 佳彦: "臍帯径の胎児発育" 産婦人科の実際. 第41. 1811-1813 (1892)

    • Related Report
      1992 Annual Research Report
  • [Publications] 岩下 光利、坂元 正一、中山 摂子、三室 卓久、安達 知子、武田 佳彦、安井 修司、永井 厚志: "IGF-Iとその結合蛋白の胎仔発育および肺成熟にあたえる影響" 日本界面医学学会雑誌. 第23. 69-71 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 武田 佳彦、高木 耕一郎: "ハイリスク妊娠・分娩と妊産婦死亡、予防、対策" 産婦人科の実際. 第41. 2061-2064 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 武田 佳彦: "ベリネイタルケア" 周産期医療の理論と実践. 60 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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