Functional analysis of SOF1 in sperm-oocyte fusion

• Project/Area Number: 18K14612
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Osaka University
• Principal Investigator: Noda Taichi 大阪大学, 微生物病研究所, 助教 (50712551)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 受精 / 精子 / 実験動物学 / 生殖生物学 / 発生工学

Outline of Final Research Achievements

So far, IZUMO1 on the sperm surface and CD9 and JUNO on the oocyte membrane have been identified as fusion-required factors. However, the molecular mechanism of sperm-oocyte fusion remains unclear. In this study, I focused on sperm oocyte-fusion required 1 (Sof1), which shows similar expression pattern with Izumo1. I revealed that Sof1 KO spermatozoa could not fertilize oocytes due to sperm-oocyte fusion defect, leading to male sterility. IZUMO1 showed the normal localization in KO spermatozoa, and KO spermatozoa could bind to the oocyte membrane. The immuno-blot analysis revealed that SOF1 remained after calcium ionophore “A23187”-induced acrosome reaction. SOF1 interacted with IZUMO1 when SOF1 and IZUMO1 were expressed in HEK293T cells. In addition, the expression of SOF1 did not affect the adhesion of IZUMO1-expressing HEK293T cells to the oocyte membrane. In conclusion, SOF1 may support sperm-oocyte membrane fusion in association with unknown factors.

Academic Significance and Societal Importance of the Research Achievements

精子IZUMO1が融合必須因子として同定されてから約15年間、融合に必須な精子側の因子は分かっていなかった。本課題において、申請者はSOF1が融合に関与する遺伝子として同定した。さらに最近、CRISPR/Cas9を用いたマウス個体レベルの表現型スクリーニングにより、申請者らはFIMP、SPACA6、TMEM95も融合に必須な因子であることを報告した。この結果は、精子と卵の融合は多くの分子が関与する複雑なメカニズムであることを示唆している。
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。

Research Products

• [Int'l Joint Research] Baylor College of Medicine(米国)
• [Journal Article] Tmprss12 is required for sperm motility and uterotubal junction migration in mice (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm－oocyte fusion in mice (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Male mice, caged in the International space station for 35 days, sire healthy offspring. (2019)
  • Author(s): Matsumura T, Noda T, Muratani M, Okada R, Yamane M, Isotani A, Kudo T, Takahashi S, Ikawa M.
  • Journal Title: Scientific Research Volume: 9 Issue: 1 Pages: 13733-13733
  • DOI: 10.1038/s41598-019-50128-w
  • NAID: 120006957452
  • Peer Reviewed / Open Access
• [Journal Article] Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice (2019)
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nine genes abundantly expressed in the epididymis are not essential for male fecundity in mice (2019)
  • Author(s): Noda T、Sakurai N、Nozawa K、Kobayashi S、Devlin D J、Matzuk M M、Ikawa M
  • Journal Title: Andrology Volume: 7 Issue: 5 Pages: 644-653
  • DOI: 10.1111/andr.12621
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] <i>Lvrn</i> expression is not critical for mouse placentation (2019)
  • Author(s): Tobita T, Kiyozumi D, Muto M, Noda T, Ikawa M.
  • Journal Title: Journal of Reproduction and Development Volume: 65 Issue: 3 Pages: 239-244
  • DOI: 10.1262/jrd.2018-157
  • NAID: 130007663049
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Seminal vesicle secretory protein 7, PATE4, is not required for sperm function but for copulatory plug formation to ensure fecundity. (2019)
  • Author(s): Noda T, Fujihara Y, Matsumura T, Oura S, Kobayashi S, Ikawa M.
  • Journal Title: Biology of reproduction Volume: 印刷中 Issue: 4 Pages: 1035-1045
  • DOI: 10.1093/biolre/ioy247
  • Peer Reviewed / Open Access
• [Journal Article] Chimeric analysis with newly established EGFP/DsRed2-tagged ES cells identify HYDIN as essential for spermiogenesis in mice (2019)
  • Author(s): Oura Seiya、Miyata Haruhiko、Noda Taichi、Shimada Keisuke、Matsumura Takafumi、Morohoshi Akane、Isotani Ayako、Ikawa Masahito
  • Journal Title: Experimental Animals Volume: 68 Issue: 1 Pages: 25-34
  • DOI: 10.1538/expanim.18-0071
  • NAID: 130007604401
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access
• [Presentation] 国際宇宙ステーションで飼育された雄マウスの精子受精能力の検討 (2019)
  • Author(s): 野田大地
  • Organizer: 第112回日本繁殖生物学会大会
• [Presentation] CRISPR/Cas9システムを用いた遺伝子改変マウス作製の現状と落とし穴 (2019)
  • Author(s): 野田大地
  • Organizer: 第66回日本実験動物学会総会
  • Invited
• [Presentation] 精巣上体で強く発現する9遺伝子は、オスの妊孕性に必須ではない (2019)
  • Author(s): 野田大地
  • Organizer: 第66回日本実験動物学会総会
• [Presentation] Male mice housed in the International Space Station sire healthy offspring (2019)
  • Author(s): Taichi Noda
  • Organizer: 52th Annual meeting, Society for the Study of Reproduction
  • Int'l Joint Research
• [Book] 完全版 ゲノム編集実験スタンダード (2019)
  • Author(s): 野田 大地、大浦 聖矢、伊川 正人
  • Total Pages: 386
  • Publisher: 羊土社
  • ISBN: 9784758122443
• [Remarks] ORCID
  • URL: https://orcid.org/0000-0003-0260-7861
• [Remarks] Researchmap
  • URL: https://researchmap.jp/taichi_noda/
• [Remarks] researchmap
  • URL: https://researchmap.jp/taichi_noda/
• [Remarks] Scopus
  • URL: https://www.scopus.com/authid/detail.uri?authorId=36183583800
• [Remarks] publons
  • URL: https://publons.com/researcher/1916340/taichi-noda/publications/