Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China; Reproductive Medicine Centre, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China; Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.
Exp Cell Res. 2021 Aug 15;405(2):112657. doi: 10.1016/j.yexcr.2021.112657. Epub 2021 May 31.
Checkpoint kinases (Chk) 1/2 are known for DNA damage checkpoint and cell cycle control in somatic cells. According to recent findings, the involvement of Chk1 in oocyte meiotic resumption and Chk2 is regarded as an essential regulator for progression at the post metaphase I stage (MI). In this study, AZD7762 (Chk1/2 inhibitor) and SB218078 (Chk1 inhibitor) were used to uncover the joint roles of Chk1/2 and differentiate the importance of Chk1 and Chk2 during oocyte meiotic maturation. Inhibition of Chk1/2 or Chk1 alone had no significant effect on germinal vesicle breakdown (GVBD) but significantly inhibited the first polar body (PB1). Interestingly, inhibition of Chk1 alone could not increase or completely block the extrusion of PB1 like Chk1/2 inhibition. Also, Chk1/2 inhibition resulted in defective meiotic spindle organization and chromosome condensation both in MI and metaphase II (MII) stages of oocytes. The location of γ-tubulin and Securin were abnormal or missing, while P38 MAPK was activated by Chk1/2 inhibition. Meanwhile, Chk1/2 inhibition reduced the percentage of the second polar body extrusion and pronuclear formation. In conclusion, our results further understand the functions and regulatory mechanism of Chk1/2 during oocyte meiotic maturation.
检查点激酶（Chk）1/2 可在体细胞中发挥 DNA 损伤检查点和细胞周期控制作用。根据最近的发现，Chk1 参与卵母细胞减数分裂恢复，Chk2 被认为是 MⅠ期后阶段进展的必要调节因子。在这项研究中，AZD7762（Chk1/2 抑制剂）和 SB218078（Chk1 抑制剂）被用于揭示 Chk1/2 的共同作用，并区分 Chk1 和 Chk2 在卵母细胞减数分裂成熟过程中的重要性。单独抑制 Chk1/2 或 Chk1 对生发泡破裂（GVBD）没有显著影响，但显著抑制了第一极体（PB1）的排出。有趣的是，与 Chk1/2 抑制相比，单独抑制 Chk1 不能增加或完全阻止 PB1 的排出。此外，Chk1/2 抑制导致减数分裂纺锤体结构和染色体凝聚在 MⅠ和 MⅡ期卵母细胞中均出现缺陷。γ-微管蛋白和 Securin 的位置异常或缺失，而 P38 MAPK 被 Chk1/2 抑制激活。同时，Chk1/2 抑制降低了第二极体排出和原核形成的百分比。总之，我们的结果进一步了解了 Chk1/2 在卵母细胞减数分裂成熟过程中的功能和调节机制。
