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Elucidating the molecular mechanisms of fertilization common to vertebrate animal models

Research Project

Project/Area Number 20KK0155
Research Category

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

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionNational Cardiovascular Center Research Institute

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, 部長 (70578848)

Co-Investigator(Kenkyū-buntansha) 伊川 正人  大阪大学, 微生物病研究所, 教授 (20304066)
江森 千紘  大阪大学, 微生物病研究所, 助教 (10868136)
櫻井 伸行  国立研究開発法人国立循環器病研究センター, 研究所, 特別研究員 (10808281)
吉田 恵一  地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 次世代がん医療開発センター 副センター長 (90365437)
Project Period (FY) 2020-10-27 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords受精 / 精子膜タンパク質 / 透明帯通過 / 受精膜融合 / 進化 / 種特異性
Outline of Research at the Start

本研究では、受精膜融合と異種間受精を制御する精子膜タンパク質の探索と機能解析を目的に、実験動物の小型魚類とマウスを用いて取り組む。国際共同研究先のウィーンバイオセンターへ出向き、研究代表者らと共同研究者が小型魚類を用いた解析を行う。研究代表者らはその成果をマウス解析へと還元することで、魚類から哺乳類までの脊椎動物間で広く保存される受精の分子メカニズムの解明に挑む。

Outline of Final Research Achievements

In this study, we focused on the function of sperm membrane proteins, such as SPACA4/Bouncer and DCST1-2, which play crucial roles in sperm passage through the oocyte’s zona pellucida and fusion with the oocyte membrane during fertilization. Because the genes analyzed are widely conserved among vertebrates, the Japanese team, including the principal investigator, used mammals as experimental models, while the international collaborating research partner used fish. Through this international collaborative research, we elucidated that part of the molecular mechanism of fertilization involving sperm membrane proteins (GPI-anchored proteins, etc.) are expressed in germ cells.

Academic Significance and Societal Importance of the Research Achievements

本国際共同研究により、脊椎動物間で保存される遺伝子の機能解析を通して、脈々と受け継がれてきた生物の「進化」と「生殖」に着目し、生命誕生の一端を明らかにした。特に、精子の卵子透明帯通過と卵子細胞膜融合に必須な遺伝子SPACA4, DCST1-2を発見した。本研究成果より生まれる実用面は、ヒトを含む脊椎動物種で広く利用できる精子受精能力の(遺伝子やタンパク質を対象とした)検査・診断マーカーや機能阻害による可逆的避妊薬の可能性を秘めている。

Report

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

    (39 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (10 results) Journal Article (15 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (7 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Remarks (7 results)

  • [Int'l Joint Research] ウィーンバイオセンター(オーストリア)

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

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] オウル大学(フィンランド)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ウィーンバイオセンター(オーストリア)

    • Related Report
      2022 Research-status 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] オウル大学(ノルウェー)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] ウィーンバイオセンター(オーストリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ウィーンバイオセンター(オーストリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Tex46 knockout male mice are sterile secondary to sperm head malformations and failure to penetrate through the zona pellucida2024

    • Author(s)
      Fujihara Y、Miyata H、Abbasi F、Larasati T、Nozawa K、Yu Z、Ikawa M、Matzuk MM.
    • Journal Title

      PNAS Nexus

      Volume: 3 Issue: 3 Pages: 108-108

    • DOI

      10.1093/pnasnexus/pgae108

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] The testis-specific E3 ubiquitin ligase RNF133 is required for fecundity in mice2022

    • Author(s)
      Nozawa K、Fujihara Y、Devlin DJ、Deras RE、Kent K、Larina IV、Umezu K、Yu Z、Sutton CM、Ye Q、Dean LK、Emori C、Ikawa M、Garcia TX、Matzuk MM.
    • Journal Title

      BMC Biology

      Volume: 20 Issue: 1 Pages: 161-161

    • DOI

      10.1186/s12915-022-01368-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Advancing ASMS with LC‐MS/MS for the discovery of novel PDCL2 ligands from DNA‐encoded chemical library selections2022

    • Author(s)
      Ye Q、Belabed H、Wang Y、Yu Z、Palaniappan M、Li JY、Kalovidouris SA、MacKenzie KR、Teng M、Young DW、Fujihara Y、Matzuk MM.
    • Journal Title

      Andrology

      Volume: - Issue: 5 Pages: 808-815

    • DOI

      10.1111/andr.13309

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PDCL2 is essential for sperm acrosome formation and male fertility in mice2022

    • Author(s)
      Fujihara Y、Kobayashi K、Abbasi F、Endo T、Yu Z、Ikawa M、Matzuk MM.
    • Journal Title

      Andrology

      Volume: - Issue: 5 Pages: 789-798

    • DOI

      10.1111/andr.13329

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9‐mediated disruption of <i>lipocalins</i> , <i>Ly6g5b</i> , and <i>Ly6g5c</i> causes male subfertility in mice2022

    • Author(s)
      Sakurai N、Fujihara Y、Kobayashi K、Ikawa M.
    • Journal Title

      Andrology

      Volume: - Issue: 5 Pages: 981-990

    • DOI

      10.1111/andr.13350

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CRISPR/Cas9-mediated genome editing reveals 12 testis-enriched genes dispensable for male fertility in mice2022

    • Author(s)
      Oyama Yuki、Miyata Haruhiko、Shimada Keisuke、Fujihara Yoshitaka、Tokuhiro Keizo、Garcia ThomasX、Matzuk MartinM、Ikawa Masahito
    • Journal Title

      Asian Journal of Andrology

      Volume: in press Issue: 3 Pages: 0-0

    • DOI

      10.4103/aja.aja_63_21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization2021

    • Author(s)
      Fujihara Yoshitaka、Herberg Sarah、Blaha Andreas、Panser Karin、Kobayashi Kiyonori、Larasati Tamara、Novatchkova Maria、Theussl Hans-Christian、Olszanska Olga、Ikawa Masahito、Pauli Andrea
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 39

    • DOI

      10.1073/pnas.2108777118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ゲノム編集技術を応用した精子受精能力の制御メカニズムの解明2021

    • Author(s)
      藤原祥高
    • Journal Title

      ゲノム編集技術を応用した製品開発とその実用化

      Volume: 1 Pages: 489-495

    • Related Report
      2020 Research-status Report
  • [Journal Article] Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets2020

    • Author(s)
      Robertson MJ, Kent K, Tharp N, Nozawa K, Dean L, Mathew M, Grimm SL, Yu Z, Legare C, Fujihara Y, Ikawa M, Sullivan R, Coarfa C, Matzuk MM, Garcia TX.
    • Journal Title

      BMC Biology

      Volume: 18 Issue: 1 Pages: 103-103

    • DOI

      10.1186/s12915-020-00826-z

    • NAID

      120006957462

    • Related Report
      2020 Research-status 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
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9-mediated genome-edited mice reveal 10 testis-enriched genes are dispensable for male fecundity2020

    • Author(s)
      Park Soojin、Shimada Keisuke、Fujihara Yoshitaka、Xu Zoulan、Shimada Kentaro、Larasati Tamara、Pratiwi Putri、Matzuk Ryan M、Devlin Darius J、Yu Zhifeng、Garcia Thomas X、Matzuk Martin M、Ikawa Masahito
    • Journal Title

      Biology of Reproduction

      Volume: 103 Issue: 2 Pages: 195-204

    • DOI

      10.1093/biolre/ioaa084

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 遺伝子改変技術を用いた疾患モデル動物開発法の進歩と循環器病研究への貢献2020

    • Author(s)
      藤原祥高
    • Journal Title

      循環器病研究の進歩

      Volume: 41 Pages: 67-74

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Screening male contraceptive targets using CRISPR/Cas9-mediated KO mice2023

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      2023 National Contraception Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanism of mammalian fertilization revealed by genome-edited mice2023

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      The Fibrobesity Visitor Program and Kontinkangas Campus Seminar Series 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanisms of mammalian spermatogenesis and fertilization revealed by genome-edited mice2023

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      The Fifth Annual David H. Yawn Commemorative Lecture
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PDCL2 is essential for sperm acrosome formation and male fertility in mice2023

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      56th Annual Meeting of the Society for the Study of Reproduction (SSR)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDCL2 is essential for sperm acrosome formation and male fertility in mice2023

    • Author(s)
      Yoshitaka Fujihara
    • Organizer
      The 22nd European Testis Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDCL2 is essential for sperm acrosome formation and male fertility in mice2023

    • Author(s)
      Haga S, Kobayashi K, Abbasi F, Endo T, Yu Z, Ikawa M, Matzuk MM, and Fujihara Y.
    • Organizer
      第70回日本実験動物学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 遺伝子改変マウスを用いた精子膜タンパク質FIMPの機能解析2020

    • Author(s)
      藤原祥高、Yonggang Lu、野田大地、大字亜沙美、Tamara Larasati、北加奈子、Zhifeng Yu、Ryan M. Matzuk、Martin M. Matzuk、伊川正人
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Research-status Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/Yoshitaka_Fujihara/?lang=japanese

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2020 Research-status Report
  • [Remarks] 国立研究開発法人国立循環器病研究センター先端医療技術開発部HP

    • URL

      https://www.ncvc.go.jp/res/divisions/amt/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Remarks] INFRAFRONTIER News

    • URL

      https://www.infrafrontier.eu/news/successful-launch-of-fibrobesity-visitor-programme-with-the-visit-of-dr-yoshitaka-fujihara/

    • Related Report
      2023 Annual Research 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/

    • Related Report
      2022 Research-status Report 2021 Research-status Report 2020 Research-status Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/Yoshitaka_Fujihara

    • Related Report
      2021 Research-status Report
  • [Remarks] 国立研究開発法人国立循環器病研究センター分子生物学部HP

    • URL

      https://www.ncvc.go.jp/res/divisions/bioscience/

    • Related Report
      2021 Research-status Report
  • [Remarks] 国立研究開発法人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/index.html

    • Related Report
      2020 Research-status Report

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Published: 2020-10-29   Modified: 2025-01-30  

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