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Analysis of the regulatory mechanism of primordial follicle growth in mouse ovaries

Research Project

Project/Area Number 18K06881
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionAichi Medical University

Principal Investigator

Komatsu Kouji  愛知医科大学, 医学部, 講師 (40456893)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords卵巣 / 原始卵胞 / エストラジオール / 卵胞 / 血管新生 / 一次卵胞
Outline of Final Research Achievements

Ovarian follicle development is coordinated by multiple factors, which sustain periodic ovulation. After the secondary follicular stage, follicle development is mainly regulated by gonadotropins. However, primordial and primary follicle development is regulated by gonadotropin-independent mechanism, and the regulatory mechanisms that govern these stages remain poorly understood. To elucidate these regulatory mechanisms, we developed mouse ovarian tissue culture and live imaging analysis methods. By these experimental methods, we clarified that the supply of serum substances from blood vessels provides the cue for the activation of dormant primordial follicles. Furthermore, we explored that 17β-estradiol suppresses the growth of primordial follicles in mouse ovaries. These results indicate that angiogenesis and the change of 17β-estradiol concentration in an ovary is physiological key factors in the regulation of primordial follicle growth.

Academic Significance and Societal Importance of the Research Achievements

本研究では17β-エストラジオール(E2)が卵巣組織内の原始卵胞の発育を抑制する事を明らかにした。E2は月経周期に伴って周期的に濃度変化する事から、卵巣内において周期的な原始卵胞の発育を制御する制御因子であると考えられる。また、申請者はエストロゲン受容体アンタゴニストであるタモキシフェンをマウス腹腔に投与する事によって生体内で原始卵胞の発育を促進する事ができることを確認した。エストロゲン阻害剤は抗癌剤として用いられているものが複数種類存在している事から、本研究の成果は既存のエストロゲン阻害剤のドラッグリポジショニングによる新しい不妊治療法の開発の可能性を示すものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Increased supply from blood vessels promotes the activation of dormant primordial follicles in mouse ovaries2020

    • Author(s)
      Komatsu K, Masubuchi S.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 66 Issue: 2 Pages: 105-113

    • DOI

      10.1262/jrd.2019-091

    • NAID

      130007830117

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 17β-エストラジオールはcathepsin阻害因子cystatin Aの発現量を制御する事によって原始卵胞の発育をコントロールしている2020

    • Author(s)
      小松 紘司
    • Organizer
      第113回日本繁殖生物学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 卵巣内における原始卵胞~一次卵胞の発育過程にはマルチステップな発育制御機構が存在する2019

    • Author(s)
      小松紘司
    • Organizer
      第112回日本繁殖生物学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 卵巣内で起こる血管新生は休眠状態の原始卵胞を活性化する2019

    • Author(s)
      小松紘司
    • Organizer
      第64回日本生殖医学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 卵母細胞-顆粒層細胞間の細胞膜融合による新規結合構造の解析2019

    • Author(s)
      小松紘司
    • Organizer
      第19回日本生殖工学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Promoting follicle development by inducing ovarian angiogenesis2019

    • Author(s)
      小松紘司
    • Organizer
      9th Federation of the Asia and Oceanian Physiological Societies
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生理活性物質徐放剤を用いた原始卵胞のin vivo activation2018

    • Author(s)
      小松紘司
    • Organizer
      第111回日本繁殖生物学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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