2. Academic Validation
  3. Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes

Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes

  • Development. 2024 Mar 15;151(6):dev202285. doi: 10.1242/dev.202285.
Si-Min Sun 1 2 3 4,  Bing-Wang Zhao 1 2 3 4,  Yuan-Yuan Li 1 2 3,  Hong-Yang Liu 5,  Yuan-Hong Xu 1 2 3 4,  Xue-Mei Yang 1 2 3 4,  Jia-Ni Guo 1 2 3 4,  Ying-Chun Ouyang 1,  Chang-Jiang Weng 5,  Yi-Chun Guan 6,  Qing-Yuan Sun 7,  Zhen-Bo Wang 1 2 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
  • 4 University of Chinese Academy of Sciences, Beijing 100101, China.
  • 5 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150069, China.
  • 6 Center for Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
  • 7 Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.
PMID: 38546043 DOI: 10.1242/dev.202285
Abstract

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating Enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating Enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Keywords

APC/C; Meiosis I arrest; Mouse oocytes; SAC; UBE2S.

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