Molecular Analysis of Spermatogonial Stem Cell Aging

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H05281
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section I
• Research Institution: Kyoto University
• Principal Investigator: Shinohara Takashi 京都大学, 医学研究科, 教授 (30322770)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Keywords: 精子形成 / 顕微授精

Outline of Final Research Achievements

We found that spermatogonial stem cells use glutamine for producing glutathione to protect themselves from damages by reactive oxygen species (ROS) produced by Nox1. They also possess stronger base excision repair activity than embryonic stem cells or somatic cells to minimize mutations. We also discovered that ROS induce Nox1 expression via translocation of BCL6B into the nucleus, which creates a postive feedback loop. In the course of our study to analyze the impact of long-term SSC culture, we accidentally found that in vitro fertilization and intrancytoplasmic sperm injection, both of which are widely used for human infertility treatment, can cause implantation failure and congenital abnormalities in F2 offspring.

Free Research Field

生殖生物学

Academic Significance and Societal Importance of the Research Achievements

現在、我が国では14人に一人が生殖補助医療により生まれている。特に顕微授精はウサギ2匹、ウシ1匹が生まれたのみで臨床応用されたことからヒトに対する十分な安全性は検討されていない。今回の研究により我々が得た精子幹細胞のもつ強い老化抵抗性の分子機構の知見は今後の臨床応用に有益なものであるが、その応用を進める一方で現在の生殖補助医療の安全性に対する再検討を呼びかける必要がある。