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Elucidation of the mechanisms of sperm-egg fusion using genetically modified mice

Research Project

Project/Area Number 20H03172
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionKumamoto University (2021-2023)
Osaka University (2020)

Principal Investigator

Noda Taichi  熊本大学, 大学院先導機構, 准教授 (50712551)

Co-Investigator(Kenkyū-buntansha) 原山 洋  神戸大学, 農学研究科, 教授 (30281140)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords受精 / 精子 / 融合 / 実験動物学 / 生殖生物学 / 発生工学
Outline of Research at the Start

哺乳類の受精は、精子が卵子細胞膜と融合して雄性染色体を卵子へ送り込むと同時に、卵子を活性化することで完了する。精子と卵子の融合に注目すると、精子側ではIZUMO1、卵子側ではCD9とJUNOが精子-卵子の融合に必須な因子として同定されているが、融合メカニズムの解明には至っていない。本課題では、配偶子融合に関わるSOF1~3の生理学的機能の解析を通して、融合における分子メカニズムの解明を試みる。本研究で得られた成果は、雄性繁殖能力を予想するための新規分子マーカー開発などに応用できる。

Outline of Final Research Achievements

Sperm bind to and fuse with eggs, leading to the fertilization. The objective of this study is to identify factors for the sperm-egg interaction using genetically modified mice. Specifically, I generated Dcst1 or Dcst2 knockout (KO) mice using CRISPR/Cas9. Female mice mated with these KO males hardly deliver the pups. When KO sperm were incubated with eggs, the KO sperm could pass through the zone pellucida and bind to eggs. However, these sperm hardly fused with eggs. These results indicate that DCST1 and DCST2, sperm proteins, are essential for sperm-egg fusion.

Academic Significance and Societal Importance of the Research Achievements

申請者や共同研究者らは、精子受精能力に関わる因子の同定を目的として、精巣で強発現する遺伝子を中心にKOマウスを作製して表現型スクリーニングを行っている。その結果、今回の成果も含めて、6つの精巣タンパク質が精子と卵の融合に必要であることを同定できた。これらの成果は、男性不妊の新たな原因遺伝子として診断・検査の対象となり、治療薬や避妊薬の開発へと繋がることが期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (29 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (8 results) (of which Invited: 4 results) Book (2 results) Remarks (4 results)

  • [Int'l Joint Research] 分子病理学研究所(IMP)(オーストリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Baylor College of Medicine(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Multiple genes in the Pate5-13 genomic region contribute to ADAM3 processing2024

    • Author(s)
      Noda Taichi、Shinohara Hina、Kobayashi Sumire、Taira Ayumu、Oura Seiya、Tahara Duri、Tokuyasu Midori、Araki Kimi、Ikawa Masahito
    • Journal Title

      Biology of Reproduction

      Volume: 110 Issue: 4 Pages: 750-760

    • DOI

      10.1093/biolre/ioae008

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The testis-, epididymis-, or seminal vesicle-enriched genes <i>Aldoart2</i>, <i>Serpina16</i>, <i>Aoc1l3</i>, and <i>Pate14</i> are not essential for male fertility in mice2023

    • Author(s)
      Noda Taichi、Taira Ayumu、Shinohara Hina、Araki Kimi
    • Journal Title

      Experimental Animals

      Volume: 72 Issue: 3 Pages: 314-323

    • DOI

      10.1538/expanim.22-0158

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction2023

    • Author(s)
      Lu Yonggang、Shimada Kentaro、Tang Shaogeng、Zhang Jingjing、Ogawa Yo、Noda Taichi、Shibuya Hiroki、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 8 Pages: 1-11

    • DOI

      10.1073/pnas.2207263120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TSKS localizes to nuage in spermatids and regulates cytoplasmic elimination during spermiation2023

    • Author(s)
      Shimada Keisuke、Park Soojin、Oura Seiya、Noda Taichi、Morohoshi Akane、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 11 Pages: 1-10

    • DOI

      10.1073/pnas.2221762120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish2022

    • Author(s)
      Noda Taichi、Blaha Andreas、Fujihara Yoshitaka、Gert Krista R.、Emori Chihiro、Deneke Victoria E.、Oura Seiya、Panser Karin、Lu Yonggang、Berent Sara、Kodani Mayo、Cabrera-Quio Luis Enrique、Pauli Andrea、Ikawa Masahito
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s42003-022-03289-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trim41 is required to regulate chromosome axis protein dynamics and meiosis in male mice2022

    • Author(s)
      Oura Seiya、Hino Toshiaki、Satoh Takashi、Noda Taichi、Koyano Takayuki、Isotani Ayako、Matsuyama Makoto、Akira Shizuo、Ishiguro Kei-ichiro、Ikawa Masahito
    • Journal Title

      PLOS Genetics

      Volume: 18 Issue: 6 Pages: e1010241-e1010241

    • DOI

      10.1371/journal.pgen.1010241

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sperm IZUMO1 Is Required for Binding Preceding Fusion With Oolemma in Mice and Rats2022

    • Author(s)
      Matsumura Takafumi、Noda Taichi、Satouh Yuhkoh、Morohoshi Akane、Yuri Shunsuke、Ogawa Masaki、Lu Yonggang、Isotani Ayako、Ikawa Masahito
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 1-10

    • DOI

      10.3389/fcell.2021.810118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice2021

    • Author(s)
      Zhang Xin、Sun Jiang、Lu Yonggang、Zhang Jintao、Shimada Keisuke、Noda Taichi、Zhao Shuqin、Koyano Takayuki、Matsuyama Makoto、Zhou Shushu、Wu Jiayan、Ikawa Masahito、Liu Mingxi
    • Journal Title

      Journal of Cell Science

      Volume: 134 Issue: 20 Pages: 1-14

    • DOI

      10.1242/jcs.259381

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Precise CAG repeat contraction in a Huntington’s Disease mouse model is enabled by gene editing with SpCas9-NG2021

    • Author(s)
      Oura Seiya、Noda Taichi、Morimura Naoko、Hitoshi Seiji、Nishimasu Hiroshi、Nagai Yoshitaka、Nureki Osamu、Ikawa Masahito
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s42003-021-02304-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-based genome editing in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction2020

    • Author(s)
      Sun Jiang、Lu Yonggang、Nozawa Kaori、Xu Zoulan、Morohoshi Akane、Castaneda Julio M、Noda Taichi、Miyata Haruhiko、Abbasi Ferheen、Shawki Hossam H、Takahashi Satoru、Devlin Darius J、Yu Zhifeng、Matzuk Ryan M、Garcia Thomas X、Matzuk Martin M、Ikawa Masahito
    • Journal Title

      Biology of Reproduction

      Volume: N/A Issue: 2 Pages: 183-194

    • DOI

      10.1093/biolre/ioaa083

    • NAID

      120007190927

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 精巣、精巣上体、あるいは精嚢腺で強発現する 4 遺伝子は雄マウスの妊孕性に必須ではない2023

    • Author(s)
      平 歩夢、篠原 日菜、荒木 喜美、野田 大地
    • Organizer
      第70回実験動物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 精巣上体で発現する複数のPateファミリー遺伝子が精子成熟のために協調して機能する2023

    • Author(s)
      篠原 日菜、荒木 喜美、伊川 正人、野田 大地
    • Organizer
      第95回日本遺伝学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 遺伝子改変マウスを用いた精嚢腺分泌タンパク質AOC1L3とPATE14の機能解析2023

    • Author(s)
      平 歩夢、荒木 喜美、野田 大地
    • Organizer
      第95回日本遺伝学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 遺伝子改変マウスを使った受精メカニズムの解明2023

    • Author(s)
      野田 大地
    • Organizer
      第38回日本生殖免疫学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 遺伝子改変マウスを用いた受精関連因子の機能解析2023

    • Author(s)
      野田 大地
    • Organizer
      日本アンドロロジー学会 第41回学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 遺伝子組換えマウスを用いた受精メカニズムの解明2022

    • Author(s)
      野田 大地
    • Organizer
      新学術領域研究(全能性プログラム、配偶子インテグリティ)、熊本大学発生医学研究所、大阪大学蛋白質研究所の共催、シンポジウム-“生殖細胞と減数分裂研究の過去、現在、未来"
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マウスとゼブラフィッシュにおいて精子膜タンパク質DCST1/2は精子と卵の相互作用に関わる2022

    • Author(s)
      野田 大地
    • Organizer
      令和3年度先端モデル動物支援 プラットホーム成果発表会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 精子-卵の融合に必須な精子タンパク質の同定2021

    • Author(s)
      野田 大地
    • Organizer
      第62回日本卵子学会学術集会、若手企画
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 最新のゲノム編集技術と用途展開2021

    • Author(s)
      野田 大地、伊川 正人
    • Total Pages
      14
    • Publisher
      シーエムシー出版
    • ISBN
      9784781315867
    • Related Report
      2020 Annual Research Report
  • [Book] マウス・ラットモデル作製・解析プロフェッショナル2021

    • Author(s)
      野田 大地、伊川 正人
    • Total Pages
      11
    • Publisher
      羊土社
    • ISBN
      9784758121125
    • Related Report
      2020 Annual Research Report
  • [Remarks] 熊本大学 生命資源研究・支援センター 生殖機能学分野 ラボHP

    • URL

      https://reproductive-biology-kuma-u.jimdofree.com/

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/taichi_noda/

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] ORCID

    • URL

      https://orcid.org/0000-0003-0260-7861

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 熊本大学 生命資源研究・支援センター 生殖機能学分野 ラボHP

    • URL

      https://reproductive-biology-kuma-u.jimdofree.com/

    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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