Functional analysis of SOF1 in sperm-oocyte fusion

2019 Fiscal Year Final Research Report

• 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
• Keywords: 受精 / 精子

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.

Free Research Field

生殖生物学

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。