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Research for elucidation of the pathogenesis of ovarian failure in terms of the mechanisms of ovarian follicle apoptosis

Research Project

Project/Area Number 12671581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

KUGU Koji  THE UNIVERSITY OF TOKYO, The University of Tokyo Obstetrics and Gynecology, Lecture (30322051)

Co-Investigator(Kenkyū-buntansha) YANO Tetsu  The University of Tokyo, Gynecilogic Surgery, Associate Professor (90251264)
MOMOEDA Mikio  The University of Tokyo, Obstetrics and Gynecology, Research Associate (50221627)
OSUGA Yutaka  The University of Tokyo, Gynecilogic Surgery, Research Associate (80260496)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsOvary / Apoptosis / Anti-cancer drug / Ovarian failure / 卵胞 / 卵子 / 黄体 / bcl-2遺伝子 / ホルモン
Research Abstract

Among the increasing number of cell death regulators that have been identified to date, members of the bcl-2 (B-cell lymphoma/leukemia-2 protein) gene family have emerged as principal players in the cascade of events that activate or inhibit apoptosis. Overexpression of bcl-2 prevents apoptotic cell death induced by various physiological, pathological, and experimental stimuli in a variety of cell types. The role of the Bcl-2 death-repressor protein in female germ cell survival has recently been proposed, and histological and morphometric studies on ovaries collected from bcl-2 gene knock-out mice have revealed reduced endowment of oocyte-containing primordial follicles in comparison with that in age-matched wild-type female mice. Although these data suggest a role for bcl-2 in oogonium and/or oocyte survival, whether bcl-2 directly represses apoptosis in germ cells as has been described in other cell systems, remains to be elucidated.
Caspases, a family of aspartic acid-specific cysteine proteases, are considered to be death effectors that possess an obligate specificity for cleavage of target proteins at aspartate residues in diverse cell lineages. They take part in the final steps of cell death committal via their unique ability to cleave a wide spectrum of homeostatic proteins. Among these targets are nuclear and cytoskeletal proteins., although it remains to be established whether cleavage of these proteins is required for the execution of all cell deaths.
Besides, docetaxel, a new anti-cancer drug, is revealed to spoil the ovum through apoptosis like other various kinds of anti-cancer drugs in this series of investigation.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (31 results)

All 2002 2001 Other

All Journal Article (14 results) Publications (17 results)

  • [Journal Article] Effects of gonadotropin-releasing hormone analog freatment on skincondition.2002

    • Author(s)
      Yutaka Osuga, Koji Kugu, et al.
    • Journal Title

      Gynecological Endocrinology 16

      Pages: 57-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Cellulor mechanisms of grmoth inhibition of human epithelial warian…2002

    • Author(s)
      Xiaohui Tang, Koji Kugu, et al.
    • Journal Title

      The Journal of Clinical Endocrinology and Metabolism 87

      Pages: 3721-3727

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] The evaluation of the sentinel nohe successfully conducted in a case of…2002

    • Author(s)
      Shunsuke Nakagawa, Koji Kugu, et al.
    • Journal Title

      Gynecologic Oncology 86

      Pages: 387-389

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(和文)」より2002

    • Author(s)
      森田豊, 久具宏司, 他
    • Journal Title

      Annual Review内分泌代謝2002分担執筆(胎児期れおける卵子数調節機序)(中外医学社)

    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Effects of gonadotropin-releasing hormone analog treatment on skin condition.2002

    • Author(s)
      Yutaka Osuga, Tetsu Yano, Koji Kugu, Kaori Koga, Kayo Fukuoka, Hirotaka Matsumi, Osamu Wada, Akihiko Kikuchi, Osamu Tsutsumi, Yuji Taketani.
    • Journal Title

      Gynecological Endocrinology 16(1)

      Pages: 57-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Cellular mechanisms of growth inhibition of human epithelial ovarian cancer cell line by LH-releasing hormone antagonist cetrorelix.2002

    • Author(s)
      Xiaohui Tang, Tetsu Yano, Yutaka Osuga, Hirotaka Matsumi, Naomi Yano, Jiping Xu, Osamu Wada, Kaori Koga, Koji Kugu, Osamu Tsutsumi, Andrew V Schally, Yuji Taketani.
    • Journal Title

      The Journal of Clinical Endocrinology and Metabolism 87(8)

      Pages: 3721-3727

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] The evaluation of the sentinel node successfully conducted in a case of malignant melanoma of the vagina.2002

    • Author(s)
      Shunsuke Nakagawa, Kaori Koga, Koji Kugu, Osamu Tsutsumi, Yuji Taketani.
    • Journal Title

      Gynecologic Oncology 86(3)

      Pages: 387-389

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Regulatory mechanisms of female germ cell apoptosis during embryonic development.2002

    • Author(s)
      Yutaka Morita, Koji Kugu, Osamu Tsutsumi, Yuji Taketani.
    • Journal Title

      Annual Review ; Endocrinology/Metabolism 2002 (Eds. Yasunori Kanazawa, Yuji Taketani, Hisahiko Sekihara, Nobuhiro Yamada). (Chugai-Igakusha, Tokyo)

      Pages: 59-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Effects of bisphosphonate on bone mineral density and biochemical bone…2001

    • Author(s)
      Koji Kugu, Tetsu Yano, et al.
    • Journal Title

      Gynecologie Endocrinlogy 15(suppll)

      Pages: 19-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Hyperemesis gravidarum associated with thyretoxicosis and a past history…2001

    • Author(s)
      Hisahiko Hiroi, Koji Kugu, et al.
    • Journal Title

      Archives of Gynecology and Obstetrics 265

      Pages: 228-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Is an elevation in basol follicle-stimulating hormone levels in unexplained…2001

    • Author(s)
      Koji Kugu, Mikio Monoeda, et al.
    • Journal Title

      Endocrine Journal 48

      Pages: 711-715

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Effects of bisphosphonate on bone mineral density and biochemical bone marker during treatment with GnRH analogues.2001

    • Author(s)
      Koji Kugu, Tetsu Yano, Yutaka Osuga, Kayo Fukuoka, Yuji Taketani.
    • Journal Title

      Gynecological Endocrinology 15(Suppl 1)

      Pages: 19-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Hyperemesis gravidarum associated with thyrotoxicosis and a past history of an eating disorder.2001

    • Author(s)
      Hisahiko Hiroi, Koji Kugu, Hiromi Hoshino, Shiro Kozuma, Yuji Taketani.
    • Journal Title

      Archives of Gynecology and Obstetrics 265(4)

      Pages: 228-230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Is an elevation in basal follicle-stimulating hormone levels in unexplained infertility predictive of fecundity regardless of age? (Endocrine Journal)2001

    • Author(s)
      Koji Kugu, Mikio Momoeda, Siya S.Sharma, Yutaka Osuga, Toshihiro Fujiwara, Hiroko Fukushima, Tetsu Yano, Osamu Tsutsumi, Yuji Taketani.
    • Journal Title

      48(6)

      Pages: 711-715

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yutaka Osuga, Koji Kugu, et al.: "Effects of gonadotropin-releasing hormone analog treatment on skin condition"Gynecological Endocrinology. 16・1. 57-61 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Xiaohui Tang, Tetsu Yano, Koji Kugu, et al.: "Cellular mechanisms of gruoth inhibition of human epithelial ouarian cancer cell line・・・・・"The Journal of Clinical Endocrinology and Metabolism. 87・8. 3721-3727 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shunsuke Nakagawa, Koji Kugu, et al.: "The evaluation of the sentinel node successfully conducted in a case・・・・・"Gynecologic Oncology. 86・3. 387-389 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akihisa Fujimoto, Mikio Momoeda, Koji Kuga, et al.: "Human chorionic gonadotropin combined with progesterone for luteal support improves・・・・・"Journal of Assisted Reproduction and Genetics. 19・12. 550-554 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田中敏章, 久具宏司, 他: "中枢性思春期早発症女児における性腺抑制療法終了後の排卵性月経の評価"ホルモンと臨床. 50・12. 1139-1144 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森田豊, 久具宏司, 他: "Annual Review内分泌・代謝2002の分担執筆(胎児期における卵子数調節機序)"中外医学社. 7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osuga Y, Kugu K, et al.: "Evidence for the presence of KGF in human ovarian follicles"Endocrine Journal. 48・2. 161-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kugu K, Yano T, et al.: "Effects of bisphosphonat on BMD and biomedical bone marker during treatment with (GnRH) analogues"Gynecological endocrinology. 15・(Suppl1). 19-19 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshiro O, Kugu K. et al.: "Evidence for the presence of IL-18 an IL-18BP expression in the human endmetrium"Molecular Human Reproduction. 7・7. 649-654 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osuga Y, Kugu K, et al.: "Usefulness of long-jaw forceps in laparoscopic conual reseclion of interstitial pregnancy"The Journal of American Association of Gynecologic Laparoscopists. 8・3. 429-432 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroi H, Kugu K, et al.: "Hyperemesis graridarum associated with thyrotoxicosis and a past history of an eating disorder"Archives of Gynecology and Obstetrics. 265・4. 228-230 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kugu K, Momoeda M, et al.: "Is an elevation in basal FSH levels in unexplained infertility predictive of fecantity regulates of age?"Endocrine Journal. 48・6. 711-715 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirotaka Matsumi,Koji Kugu, et al.: "Regulation of nitric oxide synthase to promote cytostasis in ovarian follicular"Biology of Reproduction. 63・1. 141-146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Taketani, Koji Kugu, et al: "Recent developments and dilemmas in infertility treatment."Asian Medical Journal. 43・7. 303-311 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaori Koga,Koji Kugu, et al.: "Evidence for the presence of angiogenin in human follicular fluid and the up-regulation of its production by hCG and hypoxia."The Journal of Clinical Endocrinology and Metabolism. 85・9. 3352-3355 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaori Koga,Koji Kugu, et al.: "Increased concentrations of sTNFR I and II in peritoneal fluid from women with endometriosis."Molecular Human Reproduction. 6・10. 929-933 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tetsu Yano,Koji Kugu, et al.: "Inhibition of human epithelial ovarian cancer cell growth in vitro by somatostatin analog RC-160."Oncology. 59・Suppl1. 45-49 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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