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2023 Fiscal Year Annual Research Report

Deciphering the cellular and molecular mechanisms underlying mammalian sperm-egg fusion

Research Project

Project/Area Number 22K15103
Research InstitutionOsaka University

Principal Investigator

Lu Yonggang  大阪大学, ヒューマン・メタバース疾患研究拠点, 特任准教授(常勤) (00817033)

Project Period (FY) 2022-04-01 – 2024-03-31
KeywordsFertilization / Sperm-egg fusion / Spermiogenesis / Fusogen / Male infertility / Male reproduction / Genome editing / Protein interaction
Outline of Annual Research Achievements

During this project, I have made substantial progress in understanding the mechanism of mammalian fertilization and reproduction. From April 2022 to March 2024, I have published 5 first authored papers and 3 co-authored papers in international peer reviewed journals. Among these publications, I would like to highlight 3 discoveries that are very important to the field of sperm-egg fusion. First, in collaboration with Stanford University, we elucidated the molecular function of TMEM95 in human fertilization (Tang*, Lu* et al. 2022 PNAS). Using innovative in vitro assays (such as sperm penetration assay, biolayer interferometry analysis, antibody inhibitory assay), we found that unlike IZUMO1, TMEM95 plays a critical role after sperm-egg binding and that sperm TMEM95 has a putative receptor on the egg plasma membrane. Second, I discovered a testis-specific, type-II transmembrane protein, 1700029I15Rik, that regulates the biosynthesis of acrosomal membrane glycoproteins involved in sperm-egg fusion (e.g., IZUMO1, SPACA6, EQTN; Lu et al. 2023 PNAS). This finding marks the discovery of a novel protein biosynthesis pathway underpinning the correct assembly of fertilization machinery during sperm development. Third, in collaboration with Karolinska Institutet, we deciphered the detailed structural and molecular mechanisms underlying zona pellucida block to polyspermy, which was a long-stand mystery in the field of fertilization.

  • Research Products

    (16 results)

All 2024 2023 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 4 results) Remarks (4 results)

  • [Int'l Joint Research] Yale University/University of California, Berkeley/Stanford University(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Yale University/University of California, Berkeley/Stanford University
    • # of Other Institutions
      2
  • [Int'l Joint Research] Karolinska Institutet/University of Gothenburg/Uppsala University(スウェーデン)

    • Country Name
      SWEDEN
    • Counterpart Institution
      Karolinska Institutet/University of Gothenburg/Uppsala University
  • [Int'l Joint Research] IMP(オーストリア)

    • Country Name
      AUSTRIA
    • Counterpart Institution
      IMP
  • [Journal Article] Disruption of testis-enriched cytochrome c oxidase subunit COX6B2 but not COX8C leads to subfertility2024

    • Author(s)
      Shimada Keisuke、Lu Yonggang、Ikawa Masahito
    • Journal Title

      Experimental Animals

      Volume: 73 Pages: 1~10

    • DOI

      10.1538/expanim.23-0055

    • Peer Reviewed / Open Access
  • [Journal Article] ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat2024

    • Author(s)
      Nishio Shunsuke、Emori Chihiro、Wiseman Benjamin、Fahrenkamp Dirk、Dioguardi Elisa、Zamora-Caballero Sara、Bokhove Marcel、Han Ling、Stsiapanava Alena、Algarra Blanca、Lu Yonggang、...、Ikawa Masahito、Jovine Luca
    • Journal Title

      Cell

      Volume: 187 Pages: 1440~1459.e24

    • DOI

      10.1016/j.cell.2024.02.013

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Pages: 1~11

    • DOI

      10.1073/pnas.2207263120

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ADAD2 functions in spermiogenesis and piRNA biogenesis in mice2023

    • Author(s)
      Lu Yonggang、Nagamori Ippei、Kobayashi Hisato、Kojima‐Kita Kanako、Shirane Kenjiro、Chang Hsin‐Yi、Nishimura Toru、Koyano Takayuki、Yu Zhifeng、Casta?eda Julio M.、Matsuyama Makoto、Kuramochi‐Miyagawa Satomi、Matzuk Martin M.、Ikawa Masahito
    • Journal Title

      Andrology

      Volume: 11 Pages: 698~709

    • DOI

      10.1111/andr.13400

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPR/Cas9‐mediated genome editing reveals seven testis‐enriched transmembrane glycoproteins dispensable for male fertility in mice2023

    • Author(s)
      Ogawa Yo、Lu Yonggang、Kiyozumi Daiji、Chang Hsin‐Yi、Ikawa Masahito
    • Journal Title

      Andrology

      Volume: なし

    • DOI

      10.1111/andr.13564

    • Peer Reviewed / Open Access
  • [Presentation] ADAD2 functions in spermiogenesis and piRNA biogenesis in mice2023

    • Author(s)
      Lu Yonggang、Nagamori Ippei、Kobayashi Hisato、Kojima‐Kita Kanako、Shirane Kenjiro、Chang Hsin‐Yi、Nishimura Toru、Koyano Takayuki、Yu Zhifeng、Casta?eda Julio M.、Matsuyama Makoto、Kuramochi‐Miyagawa Satomi、Matzuk Martin M.、Ikawa Masahito
    • Organizer
      The 1st Asian Congress for Reproductive Immunology (ACRI)
    • Int'l Joint Research
  • [Presentation] 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
    • Organizer
      Society for the Study of Reproduction (SSR) 56th Annual Meeting
    • Int'l Joint Research
  • [Presentation] Identification of a sperm trimeric complex essential for vertebrate fertilization2023

    • Author(s)
      Deneke Victoria E.、Lu Yonggang、Phan Clara、Draper Jonne、Vance Tyler、Blaha Andreas、Panser Karin、Stejskal Karel、Schleiffer Alexander、Kamoshita Maki、Lee Jeffrey、Ikawa Masahito、Pauli Andrea
    • Organizer
      The 24th Gordon Research Conference (GRC) on Fertilization and Activation of Development
    • Int'l Joint Research
  • [Presentation] ERP2 is required for sperm motility and male fertility in male mice2023

    • Author(s)
      Chang Hsin-Yi、Lu Yonggang、Ikawa Masahito
    • Organizer
      The 1st Asian Congress for Reproductive Immunology (ACRI)
    • Int'l Joint Research
  • [Remarks] 1700029I15Rikは精子と卵の融合に必要な先体膜タンパク質のプロセシングを制御する

    • URL

      http://www.biken.osaka-u.ac.jp/achievement/research/2023/188

  • [Remarks] ヒト精子TMEM95が卵に結合して受精融合を促進(伊川研がPNASに発表)

    • URL

      http://www.biken.osaka-u.ac.jp/achievement/research/2022/179

  • [Remarks] How the egg controls sperm entry

    • URL

      https://www.sciencedaily.com/releases/2024/03/240314122104.htm

  • [Remarks] How does the body avoid polyspermy

    • URL

      https://www.eurekalert.org/news-releases/1037730

URL: 

Published: 2024-12-25  

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