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A mechanism of uterus for sensing sperm and inflammatory response toward development of new diluent of frozen bull semen

Research Project

Project/Area Number 18K19259
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

Miyamoto Akio  帯広畜産大学, 畜産学部, 教授 (10192767)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsウシ / 子宮 / 人工授精 / 精子 / 炎症 / 凍結精液 / 炎症反応
Outline of Final Research Achievements

This study aimed to establish the basic information to develop a new diluent for cryopreserved bovine semen straws, by reducing the first inflammatory response of uterus to sperm using non-inflammatory diluent. A series of results reveals for the first time that sperm immediately enter the uterine glands and trigger uterine TLR2 signaling, thereby induce inflammatory cascade. In particular, a new ex-vivo model of uterine piece co-incubated with sperm enabled us to investigate a dynamics of sperm-uterine interaction using a video observation with protein and gene expression. Further, we established an in vivo model using a cow in which a real-time investigation of sperm and immune cell appearance immediately after artificial insemination. Altogether, we indicated the novel sperm-sensing system in the uterus that uses TLR2, by developing a new ex-vivo and in vivo model to investigate the dynamics of sperm-uterine immune-crosstalk.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ウシ子宮内免疫環境は、授精された精子によって強いTh1型(炎症性)に誘導され、そのセンシングには病原体認識と同様のTLR2/4が活用されている事実を世界で初めて実験的に示した。特にウシ子宮小片のビデオ観察を含むex-vivo新規器官培養系を確立して、視覚的に精子と子宮の相互作用のダイナミクスを初めて示したことは、ウシ人工授精の分野に重要な科学情報を示した。さらに、生体モデルで人工授精直後の子宮内免疫応答の動態をリアルタイムで観察する方法を確立できたので、今後の受胎率向上に向けた生体レベルの子宮内TLR2刺激による母体免疫活性化への道筋が初めて示された。

Report

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

    (13 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Bovine oviduct epithelial cells suppress the phagocytic activity of neutrophils towards sperm but not for bacteria in vitro: Immunofluorescence and electron microscopic observations.2020

    • Author(s)
      Marey MA, Matsukawa H, Sasaki M, Ezz MA, Yousef MA, Takahashi KI, Miyamoto A.
    • Journal Title

      Histology and Histopathology

      Volume: 35

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation2020

    • Author(s)
      Akthar I, Suarez SS, Morillo VA, Sasaki M, Ezz MA, Takahashi KI, Shimada M, Marey MA, Miyamoto A.
    • Journal Title

      Reproduction

      Volume: 159 Issue: 2 Pages: 181-192

    • DOI

      10.1530/rep-19-0414

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Roadmap to pregnancy in the first 7 days post-insemination in the cow: Immune crosstalk in the corpus luteum, oviduct, and uterus2020

    • Author(s)
      Talukder AK, Marey MA, Shirasuna K, Kusama K, Shimada M, Imakawa K, Miyamoto A.
    • Journal Title

      Theriogenology

      Volume: 148 Pages: 313-320

    • DOI

      10.1016/j.theriogenology.2020.01.071

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ovulatory follicular fluid induces sperm phagocytosis by neutrophils, but oviductal fluid around oestrus suppresses its inflammatory effect in the buffalo oviduct in vitro.2019

    • Author(s)
      Yousef MS, Abd-Elhafeez HH, Talukder AK, Miyamoto A.
    • Journal Title

      Mol Reprod Dev

      Volume: 86 Issue: 7 Pages: 835-846

    • DOI

      10.1002/mrd.23164

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLR2/4 signaling pathway mediates sperminduced inflammation in bovine endometrial epithelial cells in vitro.2019

    • Author(s)
      Ezz MA, Marey MA, Elweza AE, Kawai T, Heppelmann M, Pfarrer C, Balboula AZ, Montaser A, Imakawa K, Zaabel SM, Shimada M, Miyamoto A.
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 4 Pages: e0214516-e0214516

    • DOI

      10.1371/journal.pone.0214516

    • NAID

      120006644937

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Sensing sperm by maternal immune crosstalk: A potential mechanism for interfering with fertility in the cow.2019

    • Author(s)
      Akio Miyamoto
    • Organizer
      17th International Conference on Production Disease (ICPD), Bern, Switzerland
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 子宮と卵管の精子認識:免疫システムによる攻撃と寛容2019

    • Author(s)
      宮本明夫
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Involvement of TLR2 in sperm-oviduct epithelium interaction in bovine oviduct ex vivo: Hyaluronan fragmant as a ligand?2019

    • Author(s)
      Vernadyn Almeda Morillo
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sperm penetration into the bovine pre-ovulatory uterine glands induces TNFA in glands and triggers the inflammatory cascade.2019

    • Author(s)
      Ihshan Akthar
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Real-time investigation in vivo of sperm and neutrophils distribution in the bovine uterus after artificial insemination.2019

    • Author(s)
      Mohamed Ali Marey
    • Organizer
      第112回 日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sensing sperm by bovine uterine epithelial cells via TLR2 and TLR4 signaling pathway in vitro.2018

    • Author(s)
      Akio Miyamoto
    • Organizer
      51st Annual Meeting of Society for the Study of Reproduction
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sperm induce a pro-inflammatory response in bovine uterine epithelial cells via TLR2/4 signaling pathway in vitro.2018

    • Author(s)
      Mohamed Marey
    • Organizer
      第111回 日本繁殖生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Sperm enter bovine uterine glands ex-vivo and initiate a pro-inflammatory response.2018

    • Author(s)
      Ihshan Akthar
    • Organizer
      第111回 日本繁殖生物学会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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