Developing male contraceptives targeting sperm membrane proteins using the DEC-Tec library(Fostering Joint International Research)

2019 Fiscal Year Final Research Report

• Project/Area Number: 16KK0180
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: National Cardiovascular Center Research Institute (2019); Osaka University (2016-2017)
• 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, 室長 (70578848)
• Project Period (FY): 2017 – 2019
• Keywords: リコンビナントタンパク質 / 小分子化合物 / 男性避妊薬 / ゲノム編集マウス / 精子膜タンパク質 / 受精

Outline of Final Research Achievements

I have created more than 100 gene-knockout mice and have found many genes essential for male fertility. Because most genes are conserved between mice and humans, mice are good model animals to study reproduction. I visited the Baylor College of Medicine in the United States for about seven months and collaborated with Prof. Martin M. Matzuk in joint international research. I tried to identify small molecules bound to membrane proteins essential for male fertility using the DEC-Tec library. Moreover, I generated knockout mice using the genome editing technology CRISPR/Cas9 and discovered sperm membrane proteins that are necessary for male fertility. TMPRSS12 is required for sperm migration through the oviduct and sperm motility. FIMP and SPACA6 are indispensable for sperm-oocyte fusion. We found potential sperm targets for male contraception. This knowledge could be used to develop in vitro and in vivo infertility treatments as well as male contraceptives.

Free Research Field

生殖発生工学

Academic Significance and Societal Importance of the Research Achievements

我が国では不妊不育が社会問題となっているが、世界へ目を向けると不妊不育だけでなく避妊への研究開発も進められている。特に男性に関しては、現在のところ女性用経口避妊薬に相当する避妊薬は存在しない。本課題では、新規の受精能力に必要な精子膜タンパク質の同定とそれらに結合し機能阻害する小分子化合物の探索を試みた。本研究成果を生かして今後も国際共同研究を継続し、精子膜タンパク質を標的とした男性避妊薬の開発を行い世界的問題の解決に取り組みたい。