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Development of male contraceptives that target proteases in the epididymis

Research Project

Project/Area Number 21K19569
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionOsaka University

Principal Investigator

Miyata Haruhiko  大阪大学, 微生物病研究所, 准教授 (50604732)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords男性用避妊薬 / 精巣上体 / プロテアーゼ
Outline of Research at the Start

日本では年間約20万件もの人工妊娠中絶が行われており、その理由の1つとして望まない妊娠が挙げられる。安全で効果的な避妊法の開発や普及が急務であるが、女性用経口避妊薬が存在する一方、男性用経口避妊薬の開発は成功していない。最近、男性用避妊薬の有望な標的として、精巣上体特異的に発現するプロテアーゼが同定された。本研究では、プロテアーゼ活性を阻害する小分子化合物の探索を行い、男性用避妊薬の開発に挑む。

Outline of Final Research Achievements

Spermatozoa generated in the testis are not capable of fertilizing eggs. During the process of migration through the epididymis, spermatozoa acquire motility, the ability to migrate through the female reproductive tract, and the ability to bind to the zona pellucida (extracellular matrix surrounding eggs), and fertilization becomes possible (sperm maturation process). In this study, we found that treatment of male mice with an inhibitor of a protein involved in the sperm maturation process reduced sperm motility and binding ability to the zona pellucida, resulting in a reversible decrease in male fertility.

Academic Significance and Societal Importance of the Research Achievements

日本では年間約20万件もの人工妊娠中絶が行われており、その理由の1つとして望まない妊娠が挙げられる。米国でも約50%が予定外の妊娠とされ、約半数で人工妊娠中絶が行われている。この状況を改善するには、効果的な避妊法の開発や普及が急務である。しかし、女性用避妊薬が存在する一方、男性用避妊薬の開発は成功していない。本研究では、精子成熟過程に関与するタンパク質を標的にすれば、短期間で効果があり、かつ可逆的な男性用避妊薬の開発につながることを示せた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 Other

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

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

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Testis-enriched ferlin, FER1L5, is required for Ca <sup>2+</sup> -activated acrosome reaction and male fertility2023

    • Author(s)
      Morohoshi Akane、Miyata Haruhiko、Tokuhiro Keizo、Iida-Norita Rie、Noda Taichi、Fujihara Yoshitaka、Ikawa Masahito
    • Journal Title

      Science Advances

      Volume: 9 Issue: 4

    • DOI

      10.1126/sciadv.ade7607

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Testis‐specific proteins, TSNAXIP1 and 1700010I14RIK, are important for sperm motility and male fertility in mice2023

    • Author(s)
      Kaneda Yuki、Miyata Haruhiko、Shimada Keisuke、Oura Seiya、Ikawa Masahito
    • Journal Title

      Andrology

      Volume: - Issue: 5 Pages: 1-9

    • DOI

      10.1111/andr.13378

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TULP2 deletion mice exhibit abnormal outer dense fiber structure and male infertility2022

    • Author(s)
      Oyama Yuki、Miyata Haruhiko、Shimada Keisuke、Larasati Tamara、Fujihara Yoshitaka、Ikawa Masahito
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 21 Issue: 1 Pages: 1-8

    • DOI

      10.1002/rmb2.12467

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IRGC1, a testis-enriched immunity related GTPase, is important for fibrous sheath integrity and sperm motility in mice2022

    • Author(s)
      Kaneda Yuki、Miyata Haruhiko、Shimada Keisuke、Oyama Yuki、Iida-Norita Rie、Ikawa Masahito
    • Journal Title

      Developmental Biology

      Volume: 488 Pages: 104-113

    • DOI

      10.1016/j.ydbio.2022.05.011

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of humanized LDHC knock‐in mice as a tool to assess human LDHC‐targeting contraceptive drugs2022

    • Author(s)
      Iida‐Norita Rie、Miyata Haruhiko、Kaneda Yuki、Emori Chihiro、Noda Taichi、Nakagawa Tatsuya、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Andrology

      Volume: - Issue: 5 Pages: 1-9

    • DOI

      10.1111/andr.13359

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice2021

    • Author(s)
      Miyata Haruhiko、Oura Seiya、Morohoshi Akane、Shimada Keisuke、Mashiko Daisuke、Oyama Yuki、Kaneda Yuki、Matsumura Takafumi、Abbasi Ferheen、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 35 Pages: 1-9

    • DOI

      10.1073/pnas.2106673118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FAM71F1 binds to RAB2A and RAB2B and is essential for acrosome formation and male fertility in mice2021

    • Author(s)
      Morohoshi Akane、Miyata Haruhiko、Oyama Yuki、Oura Seiya、Noda Taichi、Ikawa Masahito
    • Journal Title

      Development

      Volume: 148 Issue: 21

    • DOI

      10.1242/dev.199644

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] SPATA33はカルシニューリンをミトコンドリアに局在させることで精子運動性を制御する2023

    • Author(s)
      宮田治彦、大浦聖矢、諸星茜、嶋田圭祐、増子大輔、大山裕貴、金田侑樹、松村貴史、Abbasi Ferheen、伊川正人
    • Organizer
      アンドロロジー学会第42回学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] SPATA33はカルシニューリンをミトコンドリアに局在させることにより精子運動性を制御する2022

    • Author(s)
      宮田治彦、大浦聖矢、諸星茜、嶋田圭祐、増子大輔、大山裕貴、金田侑樹、松村貴史、Abbasi Ferheen、伊川正人
    • Organizer
      日本アンドロロジー学会 第41回学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] SPATA33はカルシニューリンをミトコンドリアに局在させることにより精子運動性を制御する2022

    • Author(s)
      宮田治彦、大浦聖矢、諸星茜、嶋田圭祐、増子大輔、大山裕貴、金田侑樹、松村貴史、Abbasi Ferheen、伊川正人
    • Organizer
      第69回日本実験動物学会総会
    • Related Report
      2022 Research-status Report
  • [Remarks] 大阪大学微生物病研究所 遺伝子機能解析分野HP

    • URL

      https://egr.biken.osaka-u.ac.jp/achievement/original_articles

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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