OGG1 protects mouse spermatogonial stem cells from reactive oxygen species in culture

Yoshifumi Mori, Narumi Ogonuki, Ayumi Hasegawa, Mito Kanatsu-Shinohara, Atsuo Ogura, Yufeng Wang, John R. McCarrey, Takashi Shinohara

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Although reactive oxygen species (ROS) are required for spermatogonial stem cell (SSC) self-renewal, they induce DNA damage and are harmful to SSCs. However, little is known about how SSCs protect their genome during self-renewal. Here, we report that Ogg1 is essential for SSC protection against ROS. While cultured SSCs exhibited homologous recombination-based DNA double-strand break repair at levels comparable with those in pluripotent stem cells, they were significantly more resistant to hydrogen peroxide than pluripotent stem cells or mouse embryonic fibroblasts, suggesting that they exhibit high levels of base excision repair (BER) activity. Consistent with this observation, cultured SSCs showed significantly lower levels of point mutations than somatic cells, and showed strong expression of BER-related genes. Functional screening revealed that Ogg1 depletion significantly impairs survival of cultured SSCs upon hydrogen peroxide exposure. Thus, our results suggest increased expression of BER-related genes, including Ogg1, protects SSCs from ROS-induced damage.

Original languageEnglish (US)
Pages (from-to)706-716
Number of pages11
JournalBiology of reproduction
Volume104
Issue number3
DOIs
StatePublished - Mar 1 2021
Externally publishedYes

Keywords

  • base excision repair
  • Ogg1
  • reactive oxygen species
  • spermatogonia

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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