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A comprehensive study on the pathophysiology of fetal growth restriction based on the cell biological analysis of development of placental vascular system

Research Project

Project/Area Number 13470352
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SAGAWA Norimasa  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (00162321)

Co-Investigator(Kenkyū-buntansha) OGAWA Yoshihiro  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70291424)
ITOH Hiroaki  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70263085)
KARIYA Masatoshi  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90243013)
SAITOH Yoshihiko  Nara Medical University, Professor, 医学部, 教授 (30250260)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2001: ¥10,100,000 (Direct Cost: ¥10,100,000)
Keywordsbone marrow cell / fetal growth / hepatocyte / leptin / placenta / pregnancy / resistin / trophoblast / 幹細胞 / 脱落膜 / 子宮らせん動脈 / matrix metalloproteinase / 一酸化窒素(NO) / 一酸化窒素合成酵素(NOS) / 陣痛
Research Abstract

The aim of this study was to analyze the pathophysiology of intrauterine growth restriction from the view point of cell biology of the placenta. The endothelial and inducible isoforms of nitric oxide (NO) synthesizing enzyme (eNOS, INOS) were abundantly expressed in the intrauterine tissues, especially in the placental trophoblast cells. The expression of eNOS and iNOS in the placenta ore stable even after the onset of labor, suggesting that these enzymes may play some roles in the maintenance of blood flow under the influence of other vasoconstrictive substances such as prostaglandins and angiotensin II during parturision.
The aim of present study is to develop an animal model of bone marrow cells transfer into mouse placenta in the mid gestation. Mono-nuclear fraction of bone marrow cells from GFP-Tg mice (1-5x10^5 cells/3ml) were directly injected into placental portion. The 1-8% of serial section (150-200 plates/placenta) of the sampled placenta showed 1-8 GFP positive cells, approx … More imately 5% of which were positive for cytokeratin, CD34 or p57kip2, suggesting that this experimental model might be useful in the investigation of developmental process of the placenta.
Resistin, a novel peptide hormone, is specifically expressed in the adipose tissue and decreases insulin sensitivity in rodents. In the present study, we demonstrate resistin gene expression in the human placental tissue, mainly in trophoblastic cells. The resistin gene expression in term placental tissue was more prominent than was seen in the first trimester chorionic tissue. Thus, resistin is a newly isolated placental hormone in humans which may modulate insulin sensitivity during pregnancy.
We also investigated the expression of leptin, resistin and adiponectin in the growth-restricted fetuses using mouse model of maternal food restriction. Food restriction produced IUGR fetuses. Expressions of leptin, resistin, adiponectin in IUGR fetuses were approximately half of the control fetuses. The IUGR newborn rapidly catch-up the control newborn under breast feeding ad libitum, but the leptin mRNA expression in the skin of these newborns was significantly elevated as compared to that of control newborns. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Masahiro Yoshida, et al.: "Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells -Nitric oxide as a possible mediator of uterine cervical ripening-"Molecular Human Reproduction. Vol.7. 979-985 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahiro Yosida, et al.: "Prostaglandin F_<2α'> cytokines, and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibr oblast cells"Molecular Human Reproduction. Vol.8. 681-687 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Daizo Korita, et al.: "Cyclic Mechanical Stretch Augments Prostacyclin Production in Cultured Human Uterine Myometrial Cells from Pregnant Women : Possible Involvement of Up-regulation of Prostacyclin Synthase Expression"The Journal of Clinical Endocrinology & Metabolism. Vol.87. 5209-5219 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norimasa Sagawa et al.: "Role of Leptin in Pregnancy -A Review -"Trophoblast Research. Vol.16. S80-S86 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Possible Role of Placental Leptin in Pregnancy -A eview -"Endocrine. Vol.19. 65-71 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo Yura, Norimasa Sagawa, et al.: "Rsistin Is Expressed in the Human Placenta"The Journal of Clinical Endocrinology & Metabolism. Vol.88. 1394-1397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 由良茂夫, 佐川典正: "胎児発育の分子機構"胎児の成長・発達(新女性医学大系29巻)編集:中野仁雄 中山書店. 125-141 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahiro Yoshida, et al.: "Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells -Nitric oxide as a possible mediator of uterine cervical ripening-"Molecular Human Reproduction. Vol.7. 979-985 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mercy A. Nuamah, et al.: "The plasma free to total leptin ratio in pregnant women"Frontiers in Obstetrics and Gynecolgy (Proceedings of the 53rd Annual Congress of Japan Society of Obstetrics and Gynecology), Monduzzi Editore, Italy. 99-104 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koichi Terakawa, et al.: "Site-specific Augmentation of Amnion Cyclooxygenase-2 and Decidua Vera Phospholipase-A_2 Expression in Labor: Possible Contribution of Mechanical Stretch and Interleukin-1 to Amnion Prostaglandin Synthesis"Journal of the Society for Gynecologic Investigation. Vol.9. 68-74 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masahiro Yoshida, et al.: "Prostaglandin F_<2α>, cytokines, and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibr oblast cells"Molecular Human Reproduction. Vol.8. 681-687 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Daizo Korita, et al.: "Cyclic Mechanical Stretch Augments Prostacyclin Production in Cultured Human Uterine Myometrial Cells from Pregnant Women: Possible Involvement of Up-regulation of Prostacyclin Sypthase Expression"The Journal of Clinical Endocrinology & Metabolism. Vol.87. 5209-5219 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Role of Leptin in Pregnancy -A Review-"Trophoblast Research. Vol.16. S80-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al.: "Possible Role of Placental Leptin in Pregnancy -A eview-"Endocrine. Vol.19. 65-71 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeo Yura, et al.: "Rsistin Is Expressed in the Human Placenta"The Journal of Clinical Endocrinology & Metabolism. Vol.88. 1394-1397 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Norimasa Sagawa, et al. Eds. S. Suita, H. Nakano and T. Hara: "Placental Protein and Fetal Growth, in Proceedings of the 12th Fukuoka International Symposium on Perinatal Medicine, 2001"Maternity and Perinatal Care Unit Kyusyu University Hospital, Fukuoka, Japan. 59-65 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K Terakawa, H Itoh, 他5名: "Site-specific Augmentation of Amnion Cyclooxygenase-2 and Decidua Vera of Mechanical Phospholipase-A_2 Expression in Labor : Possible Contribution Stretch and Interleukin-1 to Amnion Prostaglandin Synthesis"J Soc Gynecol Invest. 9. 68-74 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M Yoshida, N Sagawa, 他8名: "Cytokines, prostaglandin F_<2a> and mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells"Mol Hum Reprod. 8. 681-687 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] D Korita, N Sagawa, 他8名: "Cyclic Mechanical Stretch Augments Prostacyclin Production in Cultured Human Uterine Myometrial Cells from Pregnant Women : Possible Involvement of UP-regulation of Prostacyclin Synthase Expression"J Clin Endocrinol Metab. 87. 5209-5219 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N Sagawa, S Yura, 他8名: "Possible Role of Placental Leptin in Pregnancy -A Review-"Endocrine. 19. 65-71 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] N Sagawa, H Itoh, 他10名: "Role of leptin in pregnancy-a review"Placenta. 23. S80-S86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S Yura, N Sagawa, 他6名: "Resistin Is Expressed in the Human Placenta"J Clin Endocrinol Metab. 88(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 由良茂夫, 佐川典正: "胎児の成長・発達(新女性医学大系29巻):「胎児発育の分子機構」"中山書店(編集:中野仁雄). 154 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takuya Inoue et al.: "Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman"European Journal of Obstetrics & Gynecology and Reproductive Biology. 195. 184-186 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahiro Yoshida et al.: "Nitric oxide increases matrix metalloproteinase-1 production in human uterine cervical fibroblast cells -Nitric oxide as a possible mediator of uterine cervical ripening-"Molecular Human Reproduction. 7. 979-985 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koichi Terakawa et al.: "Site-specific Augmentation of Amnion Cyclooxygenase-2 and Decidua Vera Phospholipase-A_2 Expression in Labor : Possible Contribution of Mechanical Stretch and Interleukin-1 to Amnion Prostaglanding Synthesis"Journal of the Society for Gynecologic Investigation. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Norimasa Sagawa et al.: "Role of Leptin in Pregnancy-A Review-"Trophoblast Research. 23(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 佐川 典正: "産婦人科領域におけるレプチンの意義"日本産科婦人科学会雑誌. 53・8. 1686-1692 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 佐川 典正: "羊膜の生物学"周産期医学. 31・5. 1007-1014 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Norimasa Sagawa et al.: "Placental Protein and Fetal Growth In : Proceedings of 12^<th> Fukuoka International Symposium on Perinatal Medicine, (pp. 59-65)"Maternity and Perinatal Care Unit Kyushu University Hospital. 7 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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