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Inhibition of survivin induces spindle disorganization, chromosome misalignment, and DNA damage during mouse embryo development.
Cell Cycle ( IF 3.4 ) Pub Date : 2020-07-20 , DOI: 10.1080/15384101.2020.1794545
Meng-Hao Pan 1 , Jia-Qian Ju 1 , Xiao-Han Li 1 , Yi Xu 1 , Jie-Dong Wang 2 , Yan-Ping Ren 2 , Xiang Lu 2 , Shao-Chen Sun 1
Affiliation  

The early embryonic development is important for the subsequent embryo implantation, and any defects in this process can lead to embryonic aneuploidy, which causes miscarriage and birth defects. Survivin is the member of inhibitor of apoptosis protein (IAP) family, and it is also an essential subunit of chromosomal passenger complex (CPC), which regulates both apoptosis and cell cycle control in many models. However, the roles of survivin in mouse early embryos remain unclear. In the present study, we showed that survivin activity was essential for mouse early embryo development. Our results showed that survivin mainly accumulated at chromosomes at metaphase stage and located at the spindle midzone at anaphase and telophase stages during the first cleavage. Loss of survivin activity led to the failure of cleavage in early mouse embryos. Further analysis indicated that survivin involved into spindle organization and chromosome alignment. Moreover, inhibition of survivin induced oxidative stress and DNA damage, showing with the increase of ROS level, the positive γH2A signal, and the increase of Rad51 level. We also observed the occurrence of autophagy and apoptosis in the survivin-inhibited embryos. In summary, our study suggested that survivin was a critical regulator for early embryo development through its regulation on spindle organization, chromosome alignment, and DNA damage.



中文翻译:

在小鼠胚胎发育过程中,抑制存活蛋白会导致纺锤体解体、染色体错位和 DNA 损伤。

早期胚胎发育对于随后的胚胎植入很重要,这个过程中的任何缺陷都可能导致胚胎非整倍体,从而导致流产和出生缺陷。Survivin 是凋亡抑制蛋白 (IAP) 家族的成员,也是染色体过客复合体 (CPC) 的重要亚基,在许多模型中调节细胞凋亡和细胞周期控制。然而,存活蛋白在小鼠早期胚胎中的作用仍不清楚。在本研究中,我们表明存活蛋白活性对小鼠早期胚胎发育至关重要。我们的结果表明,survivin 主要在染色体中期积累,并在第一次卵裂的后期和末期位于纺锤体中区。存活蛋白活性的丧失导致早期小鼠胚胎的卵裂失败。进一步分析表明survivin参与纺锤体组织和染色体排列。此外,survivin 的抑制诱导氧化应激和 DNA 损伤,随着 ROS 水平的增加、γH2A 信号的增加和 Rad51 水平的增加而表现出来。我们还观察到存活蛋白抑制胚胎中自噬和细胞凋亡的发生。总之,我们的研究表明,存活蛋白通过其对纺锤体组织、染色体排列和 DNA 损伤的调节是早期胚胎发育的关键调节剂。我们还观察到存活蛋白抑制胚胎中自噬和细胞凋亡的发生。总之,我们的研究表明,存活蛋白通过其对纺锤体组织、染色体排列和 DNA 损伤的调节是早期胚胎发育的关键调节剂。我们还观察到存活蛋白抑制胚胎中自噬和细胞凋亡的发生。总之,我们的研究表明,存活蛋白通过其对纺锤体组织、染色体排列和 DNA 损伤的调节,是早期胚胎发育的关键调节剂。

更新日期:2020-09-08
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