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The mechanism of pregnancy from the viewpoint of mutual control system of mother and embryo

Research Project

Project/Area Number 11307031
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKETANI Yuji  The University of Tokyo, Obstetrics and Gynecology, Professor, 医学部・附属病院, 教授 (10114539)

Co-Investigator(Kenkyū-buntansha) MOMOEDA Mikio  The University of Tokyo, Obstetrics and Gynecology, Lecturer, 医学部・附属病院, 助手 (50221627)
FUJII Tomoyuki  The University of Tokyo, Obstetrics and Gynecology, Assistant Proffessor, 医学部・附属病院, 講師 (40209010)
TSUTSUMI Osamu  The University of Tokyo, Obstetrics and Gynecology, Proffessor, 医学部・附属病院, 教授 (60134574)
OSUGA Yutaka  The University of Tokyo, Obstetrics and Gynecology, Lecturer, 医学部・附属病院, 助手 (80260496)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥27,380,000 (Direct Cost: ¥26,000,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2001: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥18,600,000 (Direct Cost: ¥18,600,000)
Keywordsimplantation / decidua / HLA-G / lymphocyte / angiogic factor / angiogenin / cholersterol sulfate / trophoblast / 子宮内膜 / サイトカイン / HLA-G抗原 / 卵巣 / 妊娠 / 初期胚 / 子宮内膜症 / 体外受精
Research Abstract

For the breakthrough of reproductive medicine, the comprehensive understanding on the implantation mechanism is indispensable. In this study, we focused on mutual control system of embryo and mother in the implantation phenomenon, and intended to grasp the dynamic mechanism of implantation polyphyletically.
To begin with, we examined how the peripheral blood lymphocyte and the decidual lymphocyte in the implantation site respond to a membrane bound HLA- G antigen on the villus. It was demonstrated that the secretion of the Th1 cytokine is decreased when the peripheral blood lymphocyte recognizes HLA-G, while the secretion of the Th2 cytokine is increased. On the other hand, for the decidual lymphocyte, the secretion of the Th1 cytokine is stimulated by the contact with HLA-G, while the secretion of the Th2 cytokine does not change. The differential response between the peripheral blood lymphocyte and the decidual lymphocyte may be explained by the fact that the B cell exist in the perip … More heral blood but not in decidua, and the blocking antibody crucial for the maintenance of pregnancy can be produced only by the peripheral B cell.
Next, we investigated the expression of angiogenin, the potent angiogenic substance, in the human ovaries and its regulatory mechanisms. Angiogenin was shown to be present in follicular fluid and granulosa cell obtained from the patient for in vitro fertilization and embryo transfer. In the granulosa cell culture, the secretion of angiogenin was stimulated 3 times by hCG or CAMP, 5.5 times by the hypoxia stimulation. The mRNA level of angiogenin was 12.5 times up regulated by the hypoxia stimulation.
In addition, we attempted to elucidate the physiological roles of cholesterol sulfate, which increased in the uterine endometrium at the implantation period. As a result, it was shown that cholesterol sulfate inhibited the invasion of trophoblast into the endometrium, and the mechanism of the inhibition was non-competitive inhibition of the plasmin activity. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hiroi, H.: "Differential immunolocalization of estrogen receptor alpha and beta in rat ovary and uterus"J Mol Endocrinol. 22(1). 37-44 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takai, Y.: "Estrogen receptor-mediated effects of a xenoestrogen, bisphenol A, on preimplantation mouse embryos"Biochem Biophys Res Commun. 270(3). 918-921 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanai, T.: "Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture"Mol Hum Reprod. 7(2). 195-200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanai, T.: "Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood"Am J Reprod Immunol. 45(2). 94-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osuga, Y.: "Evidence for the presence of keratinocyte growth factor (KGF) in human ovarian follicles"Endocr J. 48(2). 161-166 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koga, K.: "Demonstration of angiogenin in human endometrium and its enhanced expression in endometrial tissues in the secretory phase and the decidua"J Clin Endocrinol Metab. 86(11). 5609-5614 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroi, H., Inoue, S., Watanabe, T., Goto, W., Orimo, A., Momoeda, M, Tsutsumi, 0., Taketani, Y. and Muramatsu, M.: "Differential immunolocalization of estrogen receptor alpha and beta in rat ovary and uterus"J Mol Endocrinol. 22 (1). 37-44 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takai, Y, Tsutsumi, 0., Ikezuki, Y., Hiroi, H., Osuga, Y, Momoeda, M., Yano, T. and Taketani, Y.: "Estrogen receptor-mediated effects of a xenoestrogen, bisphenol A, on preimplantation mouse embryos"Biochem Biophys Res Commun.. 270 (3). 918-921 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanai, T, Fujii, T., Kozuma, S., Yamashita, T., Mikl, A., Kikuchi, A. and Taketani, Y.: "Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture"Mol Hum Reprod. 7 (2). 195-200 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanai, T., Fujii, T., Unno, N., Yamashita, T., Hyodo, H., Miki, A., Hamai, Y., Kozuma, S. and Taketani, Y.: "Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood"Am J Reprod Immunol. 45 (2). 94-99 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osuga, Y., Koga, K., Tsutsumi, 0., Yano, T., Kugu, K., Momoeda, M., Okagaki, R., Suenaga, A., Fujiwara, T, Fujimoto, A., Matsumi, H., Hiroi, H. and Taketani, Y.: "Evidence for the presence of keratinocyte growth factor (KGF) in human ovarian follicles"Endocr J. 48 (2). 161-166 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koga, K., Osuga, Y., Tsutsumi, 0., Yano, T., Yoshino, O., Takai, Y., Matsumi, H., Hiroi, H., Kugu, K., Momoeda, M., Fujiwara, T. and Taketani, Y.: "Demonstration of angiogenin in human endometrium and its enhanced expression in endometrial tissues in the secretory phase and the decidua"J Clin Endocrinol Metab. 86 (11). 5609-5614 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroi, H.: "Differential immunolocalization of estrogen receptor alpha and beta in rat ovary and uterus."J Mol Endocrinol. 22(1). 37-44 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takai, Y.: "Estrogen receptor-mediated effects of a xenoestrogen, bisphenol A, on preimplantation mouse embryos"Biochem Biophys Res Commun. 270(3). 918-921 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanai, T.: "Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture"Mol Hum Reprod. 7(2). 195-200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanai, T.: "Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood"Am J Reprod Immunol. 45(2). 94-99 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osuga, Y.: "Evidence for the presence of keratinocyte growth factor (KGF) in human ovarian follicles"Endocr J. 48(2). 161-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koga, K.: "Demonstration of angiogenin in human endometrium and its enhanced expression in endometrial tissues in the secretory phase and the decidua"J Clin Endocrinol Metab. 86(11). 5609-5614 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koga.K,Csuga.Y,Tsatsumi.O,Momoeda.M et al: "Evidence for the presence of angiogenin in human follicular fluid and the up-regulation of its production by human chorionic gonadotropin and hypoxia"Journal of Clinical Endocrinology & Metabolism. 85・9. 3352-3355 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsumi,H.Yano,T,Osuga,Y.Kugu.K et al: "Regulation of nitric oxide synthase to promote cytostasis in ovarian follicular development"Biology of Reproduction. 63・1. 141-146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miki,A.,Fujii,T.,Lishikawa Y,Hamai.Y et al: "Immunotherapy prevents recurrent abortion without influencing natural killer receptor status"American Journal of Reproductive Immunology. 43・2. 98-106 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takai.Y,Tsutsumi.O,Ikezuki.T,Hiroi.H et al: "Estrogen Receptor-mediated Effects of a xenoestrogen, bisphenol A, on preimplantation mouse embryos"Biochemical & Biophysical Research Communication. 270・3. 918-921 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroi.H,Momoeda.M,Yamauchi.N, et al: "An earlier menopause as clinical manifestation of granulosa-cell tumor : a case report."Journal of Obstetrics & Gynaecology Research. 26・1. 9-12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroi.H,Tsatsumi.O,Momoeda.M, et al: "Differential interactions of bisphenol A and 17beta-estradiol with estrogen receptor alpha (ERalpha) and ER beta"Endocrine Journal. 46・6. 773-778 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Igarashi T, Osuga Y, Tsutusmi O, et al.: "Expression of Ah receptor and dioxin-related genes in human uterine endometrium in women with or without endoometrisis"ENDOCR J. 46:(6). 765-772 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroi H, Tsutsumi O, Momoeda M, et al.: "Differential interactions of bisphenol A and 17 beta-estradiol with estrogen receptor alpha (ER alpha) and ER beta"ENDOCR J. 46:(6). 773-778 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uechi H, Tsutsumi O, Morita Y, et al.: "Comparison of the effects of controlled-rate cryopreservation and vitrification on 2-cell mouse embryos and their subsequest development"HUM REPROD. 14:(11). 2827-2832 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Osuga Y, Tsutsumi O, Momoeda M, et al.: "Evidence for the presence of hepatocyte growth factor expression in human ovarian follicles"MOL HUM REPROD. 5:(8). 703-707 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Osuga Y, Tsutsumi O, Okazaki R, et al.: "Hepatocyte growth factor concentrations are elevated in peritoneal fluid of women with endometriosis"HUM REPROD. 14:(6). 1611-1613 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroi H, Momorda M, Inoue S, et al.: "Stage-specific expression of estrogen receptor subtypes and estrogen responsive finger protein in preimplantational mouse embryos"ENDOCR J. 46:(1). 153-158 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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