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多嚢胞性卵巣症候群の新たな病因の解明-胎生期における性腺細胞の分化異常

Research Project

Project/Area Number 22390307
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

水沼 英樹  弘前大学, 医学(系)研究科(研究院), 教授 (10125875)

Co-Investigator(Kenkyū-buntansha) 福原 理恵  弘前大学, 医学部附属病院, 助教 (30513379)
Project Period (FY) 2010-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords多嚢胞性卵巣症候群 / AMH / 子宮低形成 / PCOS / 免疫組織 / 顆粒膜細胞
Research Abstract

本研究は多嚢胞卵巣症候群(PCOS)の発症に、胎生期における性腺細胞の分化異常、すなわち顆粒膜細胞のセルトリ細胞化が起こっているのではないかという仮説を立て、これを実証することを目的に平成23年度から3年計画でこの事業を開始した。性腺の分化異常を呈する代表的な疾患であるRokitansky-Kuster-Hauser症候群ではしばしばPCOSを伴うこと、またPCOSの病態の中心にはアンドロゲン過剰分泌が存在することが、本仮説の出発点である。そこで、本研究では、平成23年度PCOSの卵巣に発現する遺伝子を網羅的に解析し、正常排卵周期を有する女性の卵巣に発現している遺伝子との比較検討を行った。その結果、精巣組織に特異的な遺伝子で正常卵巣に比べPCOS卵巣組織に有意に高く発現している遺伝子としてINSL3、GSTA2、NEK2、 ACE 2、CITED1、 LOC81691、ZPBPなどを同定でき、逆に、KIF2C、MLF1IP、CCNB2、A_19_P0080220、AKAP9はPCOSでの発現が低下していることが示され、PCOSの卵巣では精巣に特異的な遺伝子も発現している事を示した。そこで、さらにセルトリ細胞に特異的なマーカーとされるSox9, translation initiation factor(TIF)1,TIF2が、PCOS卵巣組織で発現しているか否かを検討した。しかし、これらのマーカーは正常卵巣でも、PCOS卵巣でも同定できず、卵巣組織にはセルトリ細胞に特異的な遺伝子の発現は確認できず、本研究の仮説は成立しない事が判明した。

Current Status of Research Progress
Reason

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (31 results)

All 2011 2010

All Journal Article (14 results) (of which Peer Reviewed: 12 results) Presentation (17 results)

  • [Journal Article] Effects of Bazedoxifene on Bone Mineral Density, Bone Turnover, and Safety in Postmenopausal Japanese Women With Osteoporosis2011

    • Author(s)
      Itabashi A, Yoh K, Chines A, Miki T, Takada M, Sato H, Gorai I, Sugimoto T, Mizunuma H, Ochi H, Constantine G, Ohta H
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 26 Pages: 519-529

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Uterine and circulating natural killer cells and their roles in women with recurrent pregnancy loss, implantation failure and preeclampsia2011

    • Author(s)
      Fukui A, Funamizu A, Yokota M, Yamada K, Nakamura R, Fukuhara R, Kimura H, Mizunuma H
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 90 Pages: 105-110

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Foxp3high and Foxp3low Treg cells differentially correlate with T helper 1 and natural killer cells in peripheral blood2011

    • Author(s)
      Sung Ki Lee, Jee yun Kim, Byung Woo Jang, Sung Eun Hur, Baeg Ju Na, Millina Lee, Fukui A, Alice Gilman-Sachs, Joanne Kwak-Kim
    • Journal Title

      Human Immunology

      Volume: 72 Pages: 621-626

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An investigaton of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay2011

    • Author(s)
      Watanabe S, Tanaka A, Fujii S, Mizunuma H, Fukui A, Fukuhara R, Nakamura R, Yamada K, Tanaka I, Awata S, Nagayoshi M
    • Journal Title

      Human Reproduction

      Volume: 26 Pages: 1219-1228

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dose effects oral estradiol on bone mineral density in Japanese women withosteoporosis2010

    • Author(s)
      Mizunuma H., et al
    • Journal Title

      Climacteric

      Volume: 13 Pages: 72-83

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluctuation of Peripheral Blood T, B, and NK Cells during a Menstrual Cycle of Normal Healthy Women2010

    • Author(s)
      Lee Sk, Kim J, Jang B, Hur S, Jung U, Kil K, Na B, Lee M, Choi Y, Fukui A, Gilman-Sachs A, Kwak-Kim J
    • Journal Title

      The Journal of Immunology

      Volume: 185 Pages: 756-762

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Case of Ovarian Clear Cell Carcinoma Simultaneously Producing Parathyroid Hormone-related Protein and Granulocyte Colony-Stimulating Factor2010

    • Author(s)
      Futagami M, Yokoyama Y, Wakui M, Taniguchi R, Higuchi T, Mizunuma H
    • Journal Title

      World Journal of Oncology

      Volume: 1 Pages: 138-141

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombinant follicle-stimulating hormone for ovulation induction in Japanese patients with anti-estrogen ineffective oligo anovulatory in fertility : results of a phase II dose-response study2010

    • Author(s)
      Taketani U., et al
    • Journal Title

      Reproduction Medicine and Biology

      Volume: 9 Pages: 91-97

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recombinant follicle-stimulating hormone (folliropin alfa) versus purified urinary follicle-stimulationg hormone in a low-dose step-up regimen to induce ovulation in japanese women with anti-estrogen-ineffective oligo- or anovulatory infertility : results of a single-blind Phase III study2010

    • Author(s)
      Taketani Y, Kelly E, Yoshimura Y, Hoshiai H, Irahara M, Mizunuma H, Saito H, Andoh K, Yanaihara T
    • Journal Title

      Reproduction Medicine and Biology

      Volume: 9 Pages: 99-106

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 黄体中期子宮内膜および流産脱落膜Natural Killer細胞におけるNatural Cytotoxicity Receptors発現2010

    • Author(s)
      福井淳史, 中村理果, 山田健市, 横田恵, 福原理恵, 木村秀崇, 藤井俊策, 水沼英樹
    • Journal Title

      日本受精着床学会雑誌

      Volume: 27 Pages: 369-374

    • NAID

      10027212049

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 卵巣予備能の維持-卵巣内膜症性嚢胞の温存手術における卵胞損失について-2010

    • Author(s)
      藤井俊策, 横田恵, 福原理恵, 福井淳史, 水沼英樹
    • Journal Title

      日本エンドメトリオーシス学会会誌

      Volume: 31 Pages: 33-38

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 機能性および器質性月経困難症の治療-ドロスピレノン・エチニルエストラジオール錠の有効性と安全性2010

    • Author(s)
      百枝幹雄, 水沼英樹, 武谷雄二
    • Journal Title

      産科と婦人科

      Volume: 77 Pages: 977-988

    • Related Report
      2010 Annual Research Report
  • [Journal Article] PCOSの診断基準2010

    • Author(s)
      藤井俊策
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 62 Pages: 1001-1008

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 経皮吸収エストラジオールゲル剤を用いた凍結胚移植2010

    • Author(s)
      福井淳史, 藤井俊策, 福原理恵, 中村理果, 山田健市, 横田恵, 福山麻美, 阿部和弘, 木村秀崇, 水沼英樹
    • Journal Title

      産婦人科の実際

      Volume: 59 Pages: 1419-1426

    • Related Report
      2010 Annual Research Report
  • [Presentation] AMH(抗ミューラー管ホルモン)と骨密度の関連性についての検討2011

    • Author(s)
      飯野香理
    • Organizer
      第22回婦人科骨粗鬆症研究会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 不妊症症例に対する経膣腹腔鏡2011

    • Author(s)
      千葉仁美, 福井淳史, 松村由紀子, 横田恵, 福原理恵, 木村秀崇, 水沼英樹
    • Organizer
      第59回北日本産科婦人科学会学術講演会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 不妊症例における子宮内膜症性嚢胞に対する腹腔鏡下エタノール固定術の有用性に関する検討2011

    • Author(s)
      松村由紀子, 木村秀崇, 福井淳史, 福原理恵, 水沼英樹, 藤井俊策
    • Organizer
      第59回北日本産科婦人科学会学術講演会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Annual Research Report
  • [Presentation] 当科で経験した悪性顆粒膜細胞腫の2例2011

    • Author(s)
      田村良介, 柳田毅, 松村由紀子, 阿部和弘, 谷口綾亮, 横山良仁, 水沼英樹
    • Organizer
      第59回北日本産科婦人科学会学術講演会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Annual Research Report
  • [Presentation] NK細胞におけるNCRs発現とサイトカイン産生との関連性2011

    • Author(s)
      横田恵, 福井淳史, 船水文乃, 福原理恵, 木村秀崇, 水沼英樹
    • Organizer
      第59回北日本産科婦人科学会学術講演会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Annual Research Report
  • [Presentation] The expression of NK cell receptors and cytokines production on endome trial or decidual natural killer cells in women with recurrent pregnancy loss2011

    • Author(s)
      Fukui A, Fukuyama A, Yokota M, Nakamura R, Yamada K, Fukuhara R, Kimura H, Mizunuma H
    • Organizer
      31st Annual Meeting of The American Society for Reproductive Immunology
    • Place of Presentation
      Salt Lake City
    • Related Report
      2011 Annual Research Report
  • [Presentation] Self-administration of Heparin beginning prior to conception for Japanese women with anti-phospholipid-associated recurrent pregnancy loss2011

    • Author(s)
      Yokota M, Fukui A, Funamizu A, Fukuyama A, Fukuhara R, Kimura H, Mizunuma H
    • Organizer
      31st Annual Meeting of The American Society for Reproductive Immunology
    • Place of Presentation
      Salt Lake City
    • Related Report
      2011 Annual Research Report
  • [Presentation] 卵巣予備能評価におけるAMHの有用性2010

    • Author(s)
      福原理恵
    • Organizer
      第21回日本内分泌学会東北地方学術集会
    • Place of Presentation
      弘前市
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] The expression of natural cytotoxicity receptors and NK cell cytokines production in pregnant women with a history of recurrent pregnancy loss or pregnancy induced hypertension2010

    • Author(s)
      Fukui A, Nakamura R, Yamada K, Funamizu A, Yokota M, Fukuhara R, Kimura H, Mizunuma H
    • Organizer
      25th Annual Meeting of japan Society for Immunology of Reproduction
    • Place of Presentation
      Osaka
    • Related Report
      2010 Annual Research Report
  • [Presentation] a2V-ATPase expression on neutrophils in pregnant women with reproductive disorder2010

    • Author(s)
      Kimura H, Fukui A, Mizunuma H, Beaman K
    • Organizer
      25th Annual Meeting of japan Society for Immunology of Reproduction
    • Place of Presentation
      Osaka
    • Related Report
      2010 Annual Research Report
  • [Presentation] The expression of natural cytotoxicity receptors on natural killer cells from midsecretory endometrium and aborted decidua2010

    • Author(s)
      Fukui A, Fukuhara R, Yamada K, Nakamura R, Yokota M, Kimura H, Fujii S, Mizunuma H
    • Organizer
      20th World Congress on Fertility and Sterility
    • Place of Presentation
      Munich
    • Related Report
      2010 Annual Research Report
  • [Presentation] The expression of natural cytotoxicity receptors and NK cell cytokines production in pregnant women with a history of recurrent pregnancy loss and regnancyinduced hypertension2010

    • Author(s)
      Fukui A, Yamada K, Fukuhara R, Nakamura R, Yokota M, Kimura H, Fujii S, Mizunuma H
    • Organizer
      20th World Congress on Fertility and Sterility
    • Place of Presentation
      Munich
    • Related Report
      2010 Annual Research Report
  • [Presentation] The effect of transdermal estradiol patch or gel for endometrial preparation on the outcome of fozen/thawed embryo transfer in Japanese wome2010

    • Author(s)
      Fukuhara R, Fukui A, Nakamura R, Yamada K, Yokota M, Kimura H, Fujii S, Mizunuma H
    • Organizer
      20th World Congress on Fertility and Sterility
    • Place of Presentation
      Munich
    • Related Report
      2010 Annual Research Report
  • [Presentation] a2V-ATPase expression on neutrophils in pregnant women with reproductive disorder2010

    • Author(s)
      Kimura H, Fukui A, Fujii S, Mizunuma H, Beaman K
    • Organizer
      20th World Congress on Fertility and Sterility
    • Place of Presentation
      Munich
    • Related Report
      2010 Annual Research Report
  • [Presentation] 経皮吸収エストラジオールゲル剤は凍結胚移植に使用しうる2010

    • Author(s)
      福井淳史, 山田健市, 中村理果, 船水文乃, 松下容子, 横田恵, 福原理恵, 木村秀崇, 水沼英樹
    • Organizer
      第28回日本受精着床学会総会学術講演会
    • Place of Presentation
      横浜市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 精液洗浄遠心処理を行なわない顕微授精についての検討2010

    • Author(s)
      中村理果, 福井淳史, 山田健市, 横田恵, 福原理恵, 木村秀崇, 水沼英樹, 藤井俊策, 渡邉誠二
    • Organizer
      第28回日本受精着床学会総会学術講演会
    • Place of Presentation
      横浜市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 不妊症に対するTrans-vaginal hydrolaparoscopyの効果2010

    • Author(s)
      福井淳史, 松下容子, 福原理恵, 木村秀崇, 水沼英樹
    • Organizer
      第50回日本産科婦人科内視鏡学会
    • Place of Presentation
      東京都
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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