UBE2D3 functions in mouse oocyte meiotic maturation

Abstract

Ubiquitin-mediated proteolysis plays a critical role in meiotic cell-cycle regulation and must be tightly controlled to achieve correct chromosome segregation. While the role of E2 ubiquitin-conjugating enzymes in mitosis is well-documented, their functions in oocyte meiosis remain largely unexplored. In this study, we identified UBE2D3 as the most highly expressed E2 enzyme in mouse oocytes, which is essential for proper meiotic division. UBE2D3 depletion caused (metaphase I) MI arrest and Cyclin B1 accumulation, whereas its overexpression led to reduced Cyclin B1 levels, kinetochore-microtubule (K-MT) mis-attachments, spindle assembly checkpoint (SAC) dysfunction, and increased aneuploidy. Notably, UBE2D3 upregulation in oocytes from aged mice contributed to age-related meiotic defects, which were partially reversed by UBE2D3 knockdown or Cyclin B1 overexpression. This study underscores the importance of the UBE2D3-Cyclin B1 axis in maintaining meiotic fidelity and highlights its potential as a therapeutic target for improving oocyte quality and fertility in aged females.