Institute of Animal Physiology, Centre of Biosciences, Slovak Academy of Sciences, Šoltésovej 4, 040 00 Košice, Slovakia.
Int J Mol Sci. 2022 Mar 23;23(7):3516. doi: 10.3390/ijms23073516.
The preimplantation period of embryogenesis is crucial during mammalian ontogenesis. During this period, the mitotic cycles are initiated, the embryonic genome is activated, and the primary differentiation of embryonic cells occurs. All cellular abnormalities occurring in this period are the primary cause of fetal developmental disorders. DNA damage is a serious cause of developmental failure. In the context of DNA damage response on the cellular level, we analyzed the course of embryogenesis and phenotypic changes during the cleavage of a preimplantation embryo. Our results document that DNA damage induced before the resumption of DNA synthesis in a zygote can significantly affect the preimplantation development of the embryo. This developmental ability is related to the level of the DNA damage. We showed that one-cell embryos can correct the first cleavage cycle despite low DNA damage and incomplete replication. It seems that the phenomenon creates a predisposition to a segregation disorder of condensed chromatin that results in the formation of micronuclei in the developmental stages following the first cleavage. We conclude that zygote tolerates a certain degree of DNA damage and considers its priority to complete the first cleavage stage and continue embryogenesis as far as possible.
哺乳动物胚胎发生的着床前阶段至关重要。在此期间，启动有丝分裂周期，胚胎基因组被激活，胚胎细胞发生初步分化。此阶段发生的所有细胞异常均是导致胎儿发育障碍的主要原因。DNA 损伤是发育失败的严重原因。在细胞水平的 DNA 损伤反应背景下，我们分析了着床前胚胎卵裂过程中的胚胎发生和表型变化。我们的结果表明，在受精卵中 DNA 合成恢复之前诱导的 DNA 损伤会显著影响胚胎的着床前发育。这种发育能力与 DNA 损伤的水平有关。我们表明，尽管存在低水平的 DNA 损伤和不完全复制，单细胞胚胎仍可以纠正第一次卵裂周期。似乎这种现象会导致染色质凝聚的分离障碍，从而导致第一次卵裂后的发育阶段形成微核。我们得出结论，受精卵可以容忍一定程度的 DNA 损伤，并认为其首要任务是完成第一次卵裂阶段，并尽可能继续胚胎发生。
