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Cytokines' role, especially G-CSF and IL-6, on human ovarian function and its clinical application

Research Project

Project/Area Number 17591762
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa Medical University

Principal Investigator

MAKINODA Satoru  Kanazawa Medical University, School of Medicine, Professor (80165688)

Co-Investigator(Kenkyū-buntansha) TOMCO Waseda  Kanaawa Medical University, School of Medicine, Assistant Professor (40367488)
TOMIZAWA Hideki  Kanaawa Medical University, School of Medicine, Assistant Professor (40319059)
FUJII Ryota  Kanaawa Medical University, School of Medicine, Senior Assistant Professor (30298351)
藤田 智子  金沢医科大学, 医学部, 助手 (90350785)
吉田 勝彦  金沢医科大学, 医学部, 助手 (30220635)
井浦 俊彦  金沢医科大学, 医学部, 助教授 (40202840)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,610,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOvarian function / luteal regression, cytokine / cytokine / G-CSF / IL-6 / Real-time quantitative RT-PCR / ovulation induction / clinical trial / IL6
Research Abstract

We have revealed the effects of cytokines, especially G-CSF and IL-6 on ovarian function as follows.
1) Cyclic changes of cytokines during the normal menstrual cycle
The cyclic changes of the cytokines▲(TNF-α, IL-1β, IL-6, GM-CSF, M-CSF) in serum that were already reported to be involved in the mechanism of ovulation and G-CSF were measured during the normal menstrual cycle. Only G-CSF showed a significant increase a few days before ovulation. Although it was not significant, IL-6 showed an increase during the late luteal phase.
2) Cyclic changes of IL-6 at the human follicular wall and its relation to the luteal regression
The expression of IL-6 mRNA at the human follicular wall increased significantly in the regressing corpus luteum. Moreover, increased IL-6 protein and receptor were observed in the follicular wall of the late luteal phase. These results will contribute to elucidate the mechanism of luteal insufficiency.
3) Clinical trial to use G-CSF as a supportive drug to ovulation induction
The following clinical trials were conducted to induce ovulation in the patients of luteinized unruptured follicle (LUF). The patients who showed LUF at the last Clomiphene-hCG cycle participated in this clinical trial. Ovulation induction using Clomiphene-hCG was performed as the last cycle. In addition, G-CSF 100 μg was administered 24-48 hours before hCG. The ovulation was successfully induced at the rate of 87.1% (54/62). Since the ovulation rate of the patients before this clinical trial was 53.5 %, the rate is significantly high (p<0.01).
Our results established a new method to induce ovulation using G-CSF.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (49 results)

All 2008 2007 2006 2005

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (41 results)

  • [Journal Article] Granulocyte colony-stimulating factor(G-CSF)in the mechanism of human ovulation an the clinical usefulness2008

    • Author(s)
      Makinoda S
    • Journal Title

      Curr Med Chem 15

      Pages: 604-613

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Granulocyte colony-stimulating factor(G-CSF) in the mechanism of human ovulation an the clinical usefulness2008

    • Author(s)
      Makinoda S
    • Journal Title

      Curr Med Chem 15(6)

      Pages: 604-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 排卵誘発に関する最近の知見2007

    • Author(s)
      牧野田 知
    • Journal Title

      北産婦医会報 119

      Pages: 2-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Regulation of amphiregulin,EGFR-like factor expression by hCG in cultured human granulosa cells2007

    • Author(s)
      Negishi H
    • Journal Title

      Acta Obstet Gynecol Scand 86

      Pages: 706-710

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Regulation of amphiregulin, EGFR-like factor expression by hCG in cultured human granulosa cells2007

    • Author(s)
      Negishi H
    • Journal Title

      Acta Obstet Gynecol Scand 86(6)

      Pages: 706-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] An intravital microscopy method permitting continuous long-term observations of ovulation in vivo in the rabbit2006

    • Author(s)
      Dahm-Kahler P
    • Journal Title

      Hum Reprod 21

      Pages: 624-631

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 黄体化未破裂卵胞(LUF)に対する排卵誘発補助薬としてのG-CSFの有用性に関する研究2006

    • Author(s)
      広崎 奈津子
    • Journal Title

      金医大誌 31

      Pages: 274-280

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] An intravital microscopy method permitting continuous long-term observations of ovulation in vivo in the rabbit2006

    • Author(s)
      Dahm-Kahler P
    • Journal Title

      Hum. Reprod. 21

      Pages: 624-631

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Luteinzed unruptured Follicle(LUF)can be prevented by Granulocyte Colony-Stimulating Factor(G-CSF)2008

    • Author(s)
      Makinoda S
    • Organizer
      The 13th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Florence
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] G-CSFを用いた排卵誘発の試み2007

    • Author(s)
      牧野田 知
    • Organizer
      第11回滋賀不妊診療懇話会
    • Place of Presentation
      大津
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 排卵誘発に関する最近の知見2007

    • Author(s)
      牧野田 知
    • Organizer
      北海道産婦人科医会学術研修会
    • Place of Presentation
      札幌
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ovarian blood flow measurement and its clinical application2007

    • Author(s)
      Makinoda S
    • Organizer
      1st Sahlgrenska Metting on Reproductive Medicine and Gynecology
    • Place of Presentation
      Goteborg
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Possible involvement of interleukin-6 human luteolysis2007

    • Author(s)
      Fujii R
    • Organizer
      1st Sahlgrenska Metting on Reproductive Medicine and Gynecology
    • Place of Presentation
      Goteborg
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト黄体退行促進とinterleukin-6(IL-6)の関連について2007

    • Author(s)
      藤井 亮太
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 黄体化未破裂卵胞(LUF)に対する排卵誘発補助薬としてのG-CSFの有用性2007

    • Author(s)
      広崎 奈津子
    • Organizer
      第59回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effective treatment using Granulocyte colony-stimulating factor(G-CSF)for luteinized unruptured follicle(LUF)2007

    • Author(s)
      Makinoda S
    • Organizer
      International Federation of Fertility Societies XIX World Congress on Fertility & Sterility
    • Place of Presentation
      Durban
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Possible involvement of interleukin-6 in human luteolysis2007

    • Author(s)
      Fujii R
    • Organizer
      International Federation of Fertility Societies XIX World Congress on Fertility & Sterility
    • Place of Presentation
      Durban
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 黄体化未破裂卵胞(LUF)に対する排卵誘発補助薬としてのG-CSFの有用性に関する研究2007

    • Author(s)
      広崎 奈津子
    • Organizer
      第35回日本産科婦人科学会北陸連合地方部会
    • Place of Presentation
      富山
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 黄体化未破裂卵胞に対する排卵誘発補助薬としてのG-CSFの有用性2007

    • Author(s)
      藤井 亮太
    • Organizer
      第9回北信越立山(能登)セミナー
    • Place of Presentation
      珠洲
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 黄体化未破裂卵胞に対する排卵誘発補助薬としてのG-CSFの有用性2007

    • Author(s)
      広崎 奈津子
    • Organizer
      第51回日本生殖医学会
    • Place of Presentation
      秋田
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] G-CSF as the supportive drug in ovulation induction for LUF2007

    • Author(s)
      Fujii R
    • Organizer
      The International Ovarian Conference 2007
    • Place of Presentation
      Hakone
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ovarian blood flow measurement and its clinical application Medicine and Gynecology2007

    • Author(s)
      Makinoda S
    • Organizer
      1st Sahlgrenska Metting on Reproductive
    • Place of Presentation
      Goteborg
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Possible involvement of interleukin-6 human luteolysis2007

    • Author(s)
      Fujii R
    • Organizer
      1st Sahlgrenska Metting on Reproductive
    • Place of Presentation
      Goteborg
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effective treatment using Granulocyte colony-stimulating factor(G-CSF) for luteinized unruptured follicle(LUF)2007

    • Author(s)
      Makinoda S
    • Organizer
      International Federation of Fertility Societies XIX World Congress on Fertility & Sterility
    • Place of Presentation
      Durban
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The involvement of granulocyte colony-stimulating factor(G-CSF)in the human ovulatory process2006

    • Author(s)
      Makinoda S
    • Organizer
      12th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Florence
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Possible involvement of interleukin-6 in human luteolysis2006

    • Author(s)
      Hirosaki N
    • Organizer
      12th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Florence
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 卵巣刺激における工夫-難治性排卵障害に対して-2006

    • Author(s)
      牧野田 知
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 卵巣周期による卵巣局所サイトカイン(G-CSFとIL-6)の発現2006

    • Author(s)
      楊 賀来慧
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 排卵、黄体機能の維持におけるIL-6の重要性に関する研究-TNF-αIL-1βGM-CSFと比較して-2006

    • Author(s)
      吉田 勝彦
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト黄体退行期におけるinterleukin-6レセプター発現の変化について2006

    • Author(s)
      藤井 亮太
    • Organizer
      第58回日本産科婦人科学会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Periodic changes of interleukin-6(IL-6)and its receptors mRNAs in the human ovary-Possible involvement of IL-6 in human luteolysis-2006

    • Author(s)
      Fujii R
    • Organizer
      The International Ovarian Conference 2006
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The involvement of granulocyte colony-stimulating factor(G-CSF)in the release of a mature oocyte2006

    • Author(s)
      Fujii R
    • Organizer
      6th Sapporo International Symposium on Ovarian Function
    • Place of Presentation
      Otaru
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Interleukin-6(IL-6)と黄体退行の関連性について2006

    • Author(s)
      藤井 亮太
    • Organizer
      第54回日本産科婦人科学会北日本連合地方部会
    • Place of Presentation
      盛岡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト卵巣におけるinterleukin-6レセプター発現の変化2006

    • Author(s)
      藤井 亮太
    • Organizer
      第11回日本生殖内分泌学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The involvement of granulocyte colony-stimulating factor(G-CSF) in the human ovulatory process2006

    • Author(s)
      Makinoda S
    • Organizer
      12th World Congress of Gynecological Endocrinology
    • Place of Presentation
      Florence
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Periodic changes of interleukin-6(IL-6) and its receptors mRNAs in the human ovary-Possible involvement of IL-6 in human luteolysis-2006

    • Author(s)
      Fujii R
    • Organizer
      The International Ovarian Conference 2006
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The involvement of granulocyte colony-stimulating factor(G-CSF) in the release of a mature oocyte2006

    • Author(s)
      Fujii R
    • Organizer
      6th Sapporo International Symposium on Ovarian Function
    • Place of Presentation
      Otaru
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト卵巣におけるアクアポリンの発現について2005

    • Author(s)
      藤井 亮太
    • Organizer
      第57回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 特異的MMPインヒビター投与がラット排卵機構へ及ぼす影響について2005

    • Author(s)
      楊 賀来慧
    • Organizer
      第57回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] hCG投与後の卵巣動脈血行動態についての検討-多変量解析を用いた排卵の有無に最も関与する指標とその測定時間について-2005

    • Author(s)
      広崎 奈津子
    • Organizer
      第57回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 黄体の退行とinterleukin-6(IL-6)の関連性についての研究2005

    • Author(s)
      呂 剛
    • Organizer
      第57回日本産科婦人科学会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ovarian hemodynamics in spontaneous & induced ovulation2005

    • Author(s)
      Waseda T
    • Organizer
      The International Ovarian Conference 2005
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Possible involvement of interleukin-6 in human luteolysis2005

    • Author(s)
      Fujii R
    • Organizer
      The International Ovarian Conference 2005
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effect of a gelatinase inhibitor on the ovulatory process2005

    • Author(s)
      Fujii R
    • Organizer
      21th European Society of Human Reproduction and Embryology
    • Place of Presentation
      Copenhagen
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 特異的gelatinaseインヒビター投与による排卵への影響について2005

    • Author(s)
      藤井 亮太
    • Organizer
      第23回日本受精着床学会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 排卵機構における卵巣局所調節因子に関する研究2005

    • Author(s)
      藤井 亮太
    • Organizer
      第53回日本産科婦人科学会北日本連合地方部会
    • Place of Presentation
      福井
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ovarian hemodynamics in spontaneous & induced ovulation2005

    • Author(s)
      Waseda T
    • Organizer
      The XIXth of Asian and Oceanic Congress of Obstetrics and Gynecology
    • Place of Presentation
      Seoul
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト卵巣におけるinterleukin-6(IL-6)発現の変化2005

    • Author(s)
      藤井 亮太
    • Organizer
      第10回日本生殖内分泌学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト自然排卵周期における卵巣血行動態解析2005

    • Author(s)
      広崎 奈津子
    • Organizer
      第50回日本不妊学会
    • Place of Presentation
      熊本
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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