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

Si-Min Sun1,2,3,4, Bing-Wang Zhao1,2,3,4, Yuan-Yuan Li1,2,3

  • 1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Development (Cambridge, England)
|March 28, 2024
PubMed

Insights

The E2 ubiquitin-conjugating enzyme UBE2S is crucial for mouse oocyte maturation and fertility. Its absence causes meiosis I arrest, affecting APC/C activity and leading to early embryonic death.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Reproductive Biology

Background:

  • Protein degradation via the ubiquitin-proteasome system is vital for cell cycle regulation.
  • The anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase controlling meiosis.
  • Ubiquitin-conjugating enzyme E2 S (UBE2S) is involved in ubiquitin delivery to APC/C, but its role in oocytes is unclear.

Purpose of the Study:

  • To investigate the function of UBE2S in mouse oocyte maturation and female fertility.
  • To elucidate the molecular mechanisms by which UBE2S influences meiotic progression.

Main Methods:

  • Generation and analysis of Ube2s knockout mice.
  • Microscopic examination of oocyte spindle assembly and checkpoint dynamics.
  • Assessment of APC/C activity and substrate levels (Cyclin B1, securin).
  • Fertilization and early embryonic development studies.

Main Results:

  • Ube2s-deleted oocytes exhibited meiosis I arrest with intact spindle assembly.
  • Absence of UBE2S impaired APC/C activity, leading to high levels of Cyclin B1 and securin.
  • Homologous chromosome separation failed in Ube2s-deficient oocytes.
  • Fertilized oocytes developed to implantation but arrested and died before embryonic day 10.5.

Conclusions:

  • UBE2S plays an indispensable role in regulating mouse oocyte meiosis.
  • UBE2S is essential for proper APC/C function, homologous chromosome separation, and female fertility.
  • Disruption of UBE2S function leads to early embryonic lethality.

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