College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
Aging (Albany NY). 2020 Jun 2;12(11):10415-10426. doi: 10.18632/aging.103267.
The quality of the early embryo is critical for embryonic development and implantation. Errors during cleavage lead to aneuploidy in embryos. As a cell cycle checkpoint protein, CHK2 participates in DNA replication, cell cycle arrest and spindle assembly. However, the functions of CHK2 in early development of the mouse embryo remain largely unknown. In this study, we show that CHK2 is localized on the spindle in metaphase and mainly accumulates at spindle poles in anaphase/telophase during the first cleavage of the mouse embryo. CHK2 inhibition led to cleavage failure in early embryonic development, accompanied by abnormal spindle assembly and misaligned chromosomes. Moreover, the loss of CHK2 activity increased the level of cellular DNA damage, which resulted in oxidative stress. Then, apoptosis and autophagy were found to be active in these embryos. In summary, our results suggest that CHK2 is an essential regulator of spindle assembly and DNA repair during early embryonic development in mice.
胚胎早期的质量对胚胎发育和着床至关重要。卵裂过程中的错误会导致胚胎非整倍体。CHK2 作为细胞周期检查点蛋白，参与 DNA 复制、细胞周期停滞和纺锤体组装。然而，CHK2 在小鼠胚胎早期发育中的功能在很大程度上仍不清楚。在这项研究中，我们发现 CHK2 在中期定位于纺锤体上，在小鼠胚胎第一次卵裂的后期/末期主要聚集在纺锤体两极。CHK2 抑制导致早期胚胎发育中的卵裂失败，伴随着异常的纺锤体组装和染色体排列不齐。此外，CHK2 活性的丧失增加了细胞 DNA 损伤水平，导致氧化应激。然后发现这些胚胎中细胞凋亡和自噬活跃。总之，我们的研究结果表明，CHK2 是小鼠早期胚胎发育中纺锤体组装和 DNA 修复的必需调节因子。
