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Analysis of possible mechanism of miscarriage in women with septate uterus

Research Project

Project/Area Number 18K09304
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNippon Medical School

Principal Investigator

Takeshita Toshiyuki  日本医科大学, 大学院医学研究科, 大学院教授 (60188175)

Co-Investigator(Kenkyū-buntansha) 桑原 慶充  日本医科大学, 医学部, 准教授 (40373013)
根岸 靖幸  日本医科大学, 医学部, 准教授 (50644580)
小野 修一  日本医科大学, 医学部, 講師 (80465301)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords中隔子宮 / 不育症 / 流産 / 樹状細胞 / ケモカイン / ケモカインレセプター / 子宮鏡下中隔切除術 / CD141+ 樹状細胞(DC) / RANTES / 着床不全 / 子宮形成術 / 樹状細胞遊走因子 / 子宮筋層 / NKT細胞
Outline of Final Research Achievements

Septate uterus is associated with spontaneous abortion. However, immunological mechanisms for miscarriage in patients with septate uterus remain completely unknown. Immune cells, dendritic cells (DCs), macrophages, T cells, natural killer cells, invariant natural killer cells, and chemokine receptors in US and uterine myometrium tissue (UMT) were analyzed using flow cytometry and immunohistochemical staining. The percentage of CD141+ DCs in US was significantly lower than that in UMT. Both US and UMT showed CCR1 and CCR5 expression on CD141+ DCs; however, the production of chemokines, MIP-1α, RANTES, and MIP-3β was abundant in UMT-obtained viable cells. The accumulation of CD141+ DCs was lower in US than that in UMT. This phenomenon may be caused by low chemokine productions in US. Our findings support the benefit of surgical intervention for septate uterus-that is, the elimination of inappropriate implantation sites.

Academic Significance and Societal Importance of the Research Achievements

中隔子宮は流産や不育症の原因になると言われているが、そのメカニズムは明らかになっていなかった。本研究では免疫学的なアプローチによりそのメカニズムの一端を解明することができた。
近年、適切な炎症は着床、妊娠初期に必要である事が報告されている。中隔子宮に対する手術療法の意義も明らかでなかったが、炎症性CD141+ DCsの欠如した中隔部を切除することは、本来起こるべき適切な炎症反応が起こらない部位を切除するという意味において、手術療法の妥当性を裏付けることになった。

Report

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

    (14 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Distribution of dendritic cells in the septate uterus: An immunological perspective.2020

    • Author(s)
      Negishi Y1,2, Kato M2, Ono S2, Kuwabara Y2, Morita R1, Takahashi H1, Takeshita T2.
    • Journal Title

      Am J Reprod Immunol.

      Volume: e13241 Issue: 6

    • DOI

      10.1111/aji.13241

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation2020

    • Author(s)
      Negishi Yasuyuki、Shima Yoshio、Takeshita Toshiyuki、Morita Rimpei
    • Journal Title

      Immunological Medicine

      Volume: - Issue: 2 Pages: 1-18

    • DOI

      10.1080/25785826.2020.1809951

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is hysteroscopic metroplasty using the incision method for septate uterus a risk factor for adverse obstetric outcomes?2019

    • Author(s)
      Ono Shuichi、Kuwabara Yoshimitsu、Matsuda Shigeru、Yonezawa Mirei、Watanabe Kenichiro、Akira Shigeo、Takeshita Toshiyuki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 45 Issue: 3 Pages: 634-639

    • DOI

      10.1111/jog.13884

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 中隔子宮と流産-免疫学的メカニズムから考察する2020

    • Author(s)
      根岸靖幸1, 2、加藤雅彦2、森田林平1、竹下俊行2
    • Organizer
      第72回日本産科婦人科学会:2020/4/23-4/287
    • Related Report
      2020 Annual Research Report
  • [Presentation] 中隔子宮における自然免疫の役割〜免疫学的見地から中隔子宮と不育症の関係を考える2020

    • Author(s)
      根岸靖幸1, 2、小野修一2、森田林平1、竹下俊行2
    • Organizer
      第2回日本不育症学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 中隔子宮における流産発症メカニズムの免疫学的考察2020

    • Author(s)
      根岸 靖幸1,2、加藤 雅彦2、竹下 俊行2、森田 林平
    • Organizer
      第48回日本臨床免疫学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 免疫学的考察による中隔子宮の流産発症機構2020

    • Author(s)
      根岸 靖幸1,2、加藤 雅彦2、森田 林平1、竹下 俊行2
    • Organizer
      第65回日本生殖医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 免疫学的知見による新しい流早産発症メカニズムの解明2020

    • Author(s)
      根岸靖幸1、加藤雅彦2、島義雄3、市川智子2、竹下俊行2、森田林平1、高橋秀実1
    • Organizer
      第47回日本臨床免疫学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Septate uterus and recurrent pregnancy loss: An immunological perspective2020

    • Author(s)
      Masahiko Kato1, Yasuyuki Negishi1,2, Tomoko Ichikawa1, Hidemi Takahashi2, Toshiyuki Takeshita1
    • Organizer
      第33回日本生殖免疫学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Is hysteroscopic metroplasty using the incision method for septate uterus a risk factor for adverse obstetric outcomes?2019

    • Author(s)
      Toshiyuki Takeshita, M.D., Ph.D., Shuichi Ono, M.D., Ph.D.,
    • Organizer
      ESGE_28th Annual Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunological aspect of uterine septum in women with recurrent pregnancy loss2019

    • Author(s)
      Toshiyuki Takeshita1, Ph.D. Yasuyuki Negishi 1,2, Masahiko Kato1, Shuichi Ono1, Hidemi Takahashi
    • Organizer
      ISIR 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中隔子宮における免疫細胞の分布~免疫学的知見よりみた中隔子宮と不育症の関係2018

    • Author(s)
      加藤雅彦、第33回日本生殖免疫学会、2018/11/24-25, 国内.
    • Organizer
      第30回日本生殖免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 18.Hysteroscopic Metroplasty for Septate Uterus2018

    • Author(s)
      Toshiyuki Takeshita
    • Organizer
      Asia-Pacific Association for Gynecologic Endoscopy and Minimally Invasive Therapy(19th) 2018/11
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 不育症2020

    • Author(s)
      竹下 俊行、藤井 知行、山田 秀人
    • Total Pages
      248
    • Publisher
      メジカルビュー社
    • ISBN
      9784758319966
    • Related Report
      2020 Annual Research Report

URL: 

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

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