The histone demethylase FBXL10 regulates the proliferation of spermatogonia and ensures long-term sustainable spermatogenesis in mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860157
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: The University of Tokyo
• Principal Investigator: Manabu Ozawa 東京大学, 医科学研究所, 助教 (80608787)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 精子形成 / 細胞周期 / 生殖細胞 / エピジェネティクス

Outline of Final Research Achievements

In this study, we show the important roles of FBXL10 as a histone demethylase in sustainable sperm production using mice in which the JmjC domain of Fbxl10 was deleted (Fbxl10 KO). In histological analysis, testes from 7-month-old Fbxl10 KO mice contained a greater ratio of seminiferous tubules exhibiting degeneration of spermatogenesis. Further analysis using an in vitro spermatogonia culture system (germline stem cells (GSCs)) revealed that Fbxl10 KO GSCs expressed a significantly higher level of P21 and P19 mRNA than wild-type (WT) GSCs. Furthermore, the doubling speed of Fbxl10 KO GSCs was significantly slower than that of WT GSCs. In addition, an in vivo study indicated that recovery of spermatogenesis after a transient reduction in the number of testicular germ cells by busulfan treatment was significantly slower in Fbxl10 KO mice than in WT mice. These data suggest that Fbxl10 plays important roles in long-term sustainable spermatogenesis via regulating cell cycle.

Free Research Field

発生工学