Elucidating the universality and specificity of reproductive mechanisms between species using genetically modified animals

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02397
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: National 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)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ゲノム編集 / 雄性不妊 / 哺乳類精子 / 小分子化合物 / 遺伝子保存

Outline of Final Research Achievements

In this study, we elucidated the functions of genes (Lcn5-10, Ly6g5b/c, Spaca4, Tex46, Dcst1/2, etc.) in male reproduction that were identified through essential gene screening using the genome editing technology CRISPR/Cas9. This discovery has offered new insights into the crucial steps involved in the fertilization process of mammalian spermatozoa, including sperm maturation through the epididymis, passage through the zona pellucida (ZP), and sperm-oocyte membrane fusion. While it is known that the sperm head shape and motility are important for passage through the ZP, little is known about the molecular interactions. We discovered that two molecules, SPACA4 and TEX46, are essential for ZP penetration in mice.

Free Research Field

生殖発生工学

Academic Significance and Societal Importance of the Research Achievements

本研究では、哺乳類生殖の中でも受精へ至るまでに精子が受精能力を獲得して卵子と膜融合するまでに必要な遺伝子群の発見に成功した。これまで不明だった精子の透明帯通過に寄与する精子膜タンパク質SPACA4, TEX46の同定は、分子機構の全容解明への第一歩となる。今回発見した因子を標的に、男性不妊の原因究明や検査・診断法の開発に繋がり、精巣上体分泌因子を用いた精子受精能力の制御や試験管内再現への可能性を秘めている。