State Key Laboratory of Reproductive Medicine and Offspring Health, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Nanjing, China.
Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
Mol Cell Proteomics. 2024 Aug;23(8):100813. doi: 10.1016/j.mcpro.2024.100813. Epub 2024 Jul 15.
Chromatin configuration serves as a principal indicator of GV (germinal vesicle)-stage oocyte quality. However, the underlying mechanisms governing the chromatin configuration transition from NSN (non-surrounded nucleolus) to SN (surrounded nucleolus) remain unclear. In this study, by conducting a quantitative proteomic analysis, we identified an increased expression of the MIB2 (MIB E3 ubiquitin protein ligase 2) protein in SN oocytes. Specific depletion of MIB2 in SN oocytes not only leads to severe disruption of the meiotic apparatus and a higher incidence of aneuploidy but also adversely affects meiotic maturation and early embryo development. Notably, overexpression of MIB2 in NSN oocytes facilitates the chromatin configuration transition. Meantime, we observed that forced expression of MIB2 in NSN oocytes significantly mitigates spindle/chromosome disorganization and aneuploidy. In summary, our results suggest that chromatin configuration transition regulated by MIB2 is crucial for oocytes to acquire developmental competence.
染色质构象是卵母细胞 GV(生发泡)期质量的主要指标。然而,调控染色质构象从 NSN(非包围核仁)向 SN(包围核仁)转变的潜在机制尚不清楚。在这项研究中,通过进行定量蛋白质组学分析,我们发现 SN 期卵母细胞中 MIB2(MIB E3 泛素蛋白连接酶 2)蛋白的表达增加。SN 期卵母细胞中 MIB2 的特异性耗竭不仅导致减数分裂装置严重破坏和非整倍体发生率增加,而且还对减数分裂成熟和早期胚胎发育产生不利影响。值得注意的是,MIB2 在 NSN 期卵母细胞中的过表达有助于染色质构象的转变。同时,我们观察到,在 NSN 期卵母细胞中强制表达 MIB2 可显著减轻纺锤体/染色体紊乱和非整倍体。总之,我们的结果表明,MIB2 调控的染色质构象转变对于卵母细胞获得发育能力至关重要。