Comprehensive elucidation of the gamete fusion mechanism in fertilization

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02453
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Inoue Naokazu 福島県立医科大学, 医学部, 准教授 (50379096)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 受精 / 精子 / 卵子 / 配偶子融合 / 膜融合 / DCST1/2

Outline of Final Research Achievements

The gamete fusion, which is the climax of fertilization, is presumably activated by the interaction between IZUMO1 on the sperm side and JUNO on the oocyte side, followed by an intermolecular reaction consisting of multiple factors, including the IZUMO1 second receptor on the oocyte. In this study, we newly identified the sperm factors DCST1 and DCST2, which are conserved as essential fertilization factors in invertebrates, in mice and humans, and found that Dcst1/2-deficient mice are completely male sterile due to gamete fusion failure, as in nematodes and flies. The analysis of the detailed molecular mechanisms involved in the DCST1/2 molecule, which has been conserved over nearly one billion years of evolution, is expected to greatly advance the study of fertilization.

Free Research Field

生殖生物学

Academic Significance and Societal Importance of the Research Achievements

現在、我が国では5.5組に1組のカップルが不妊症に悩まされており、2019年の出生児のうち14人に1人が体外受精児である。さらに2022年度より不妊治療が保険適応されたように、受精研究の社会的関心は非常に高く、晩婚化が進む中、不妊症は増加傾向にあるため、受精の分子メカニズムの解明が早急に求められている。本研究では、受精の核となる配偶子融合の必須因子を新たに同定することに成功した。この研究成果は、学術的意義のみならず、社会的意義に対する波及効果が大きいものと考えられる。