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Developing male contraceptives targeting sperm membrane proteins using the DEC-Tec library(Fostering Joint International Research)

Research Project

Project/Area Number 16KK0180
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Laboratory animal science
Research InstitutionNational Cardiovascular Center Research Institute (2019)
Osaka University (2016-2017)

Principal Investigator

Fujihara Yoshitaka  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (70578848)

Project Period (FY) 2017 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywordsリコンビナントタンパク質 / 小分子化合物 / 男性避妊薬 / ゲノム編集マウス / 精子膜タンパク質 / 受精 / 避妊薬 / DNAエンコードライブラリー
Outline of Final Research Achievements

I have created more than 100 gene-knockout mice and have found many genes essential for male fertility. Because most genes are conserved between mice and humans, mice are good model animals to study reproduction. I visited the Baylor College of Medicine in the United States for about seven months and collaborated with Prof. Martin M. Matzuk in joint international research. I tried to identify small molecules bound to membrane proteins essential for male fertility using the DEC-Tec library. Moreover, I generated knockout mice using the genome editing technology CRISPR/Cas9 and discovered sperm membrane proteins that are necessary for male fertility. TMPRSS12 is required for sperm migration through the oviduct and sperm motility. FIMP and SPACA6 are indispensable for sperm-oocyte fusion. We found potential sperm targets for male contraception. This knowledge could be used to develop in vitro and in vivo infertility treatments as well as male contraceptives.

Academic Significance and Societal Importance of the Research Achievements

我が国では不妊不育が社会問題となっているが、世界へ目を向けると不妊不育だけでなく避妊への研究開発も進められている。特に男性に関しては、現在のところ女性用経口避妊薬に相当する避妊薬は存在しない。本課題では、新規の受精能力に必要な精子膜タンパク質の同定とそれらに結合し機能阻害する小分子化合物の探索を試みた。本研究成果を生かして今後も国際共同研究を継続し、精子膜タンパク質を標的とした男性避妊薬の開発を行い世界的問題の解決に取り組みたい。

Report

(2 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (16 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] ベイラー医科大学(米国)2018

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice2020

    • Author(s)
      Fujihara Yoshitaka、Lu Yonggang、Noda Taichi、Oji Asami、Larasati Tamara、Kojima-Kita Kanako、Yu Zhifeng、Matzuk Ryan M.、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 17 Pages: 9393-9400

    • DOI

      10.1073/pnas.1917060117

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice2020

    • Author(s)
      Taichi Noda, Yonggang Lu, Yoshitaka Fujihara, View ORCID ProfileSeiya Oura, View ORCID ProfileTakayuki Koyano, Sumire Kobayashi, Martin M. Matzuk, and View ORCID ProfileMasahito Ikawa
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 21 Pages: 11493-11502

    • DOI

      10.1073/pnas.1922650117

    • NAID

      120006957465

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tmprss12 is required for sperm motility and uterotubal junction migration in mice2020

    • Author(s)
      §Larasati T., §Noda T., Fujihara Y., Shimada K., Tobita T., Yu Z., Matzuk M.M., Ikawa M.
    • Journal Title

      Biology of Reproduction

      Volume: - Issue: 2 Pages: 254-263

    • DOI

      10.1093/biolre/ioaa060

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice†2019

    • Author(s)
      Yonggang Lu, Oura Seiya, Matsumura Takafumi, et al.
    • Journal Title

      Biology of Reproduction

      Volume: 101 Issue: 2 Pages: 501-511

    • DOI

      10.1093/biolre/ioz103

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice2019

    • Author(s)
      Fujihara Yoshitaka、Noda Taichi、Kobayashi Kiyonori、Oji Asami、Kobayashi Sumire、Matsumura Takafumi、Larasati Tamara、Oura Seiya、Kojima-Kita Kanako、Yu Zhifeng、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 37 Pages: 18498-18506

    • DOI

      10.1073/pnas.1908736116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Analysis of mouse models of male infertility using genetic modification2019

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      Oulu University Kontinkangas Campus Seminar Series
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice2019

    • Author(s)
      Yoshitaka Fujihara, Asami Oji, Kanako Kita, Tamara Larasati, and Masahito Ikawa
    • Organizer
      The XXV North American Testis Workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝子改変マウスを用いた精子GPIアンカータンパク質LYPD4の機能解析2019

    • Author(s)
      藤原 祥高、大字 亜沙美、Tamara Larasati、北 加奈子、伊川 正人
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice2019

    • Author(s)
      Yoshitaka Fujihara, Asami Oji, Kanako Kita, Tamara Larasati, and Masahito Ikawa
    • Organizer
      The 52th SSR Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 精子膜タンパク質CMTM2A及びCMTM2Bの共発現がADAM3の局在と精子受精能に必須である2019

    • Author(s)
      藤原 祥高、大字 亜沙美、Tamara Larasati、北 加奈子、伊川 正人
    • Organizer
      第112回日本日本繁殖生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Sperm GPI-anchored protein LYPD4 is required for sperm migration through the oviduct in mice2019

    • Author(s)
      Yoshitaka Fujihara, Asami Oji, Tamara Larasati, Kanako Kita, Zhifeng Yu, Martin M. Matzuk and Masahito Ikawa
    • Organizer
      NICHD 2019 Contraceptive Development Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice2019

    • Author(s)
      Yoshitaka Fujihara, Asami Oji, Kanako Kita, Tamara Larasati, and Masahito Ikawa
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/Yoshitaka_Fujihara/

    • Related Report
      2019 Annual Research Report
  • [Remarks] ORCID

    • URL

      https://orcid.org/0000-0001-8332-3507

    • Related Report
      2019 Annual Research Report
  • [Remarks] 国立循環器病研究センター分子生物学部HP

    • URL

      http://www.ncvc.go.jp/res/divisions/bioscience/fujihara.html

    • Related Report
      2019 Annual Research Report

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Published: 2017-03-15   Modified: 2021-02-19  

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