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.

Department of Cell Biology Faculty of Science Charles University Viničná 7 128 00 Prague Czech Republic

Institute of Animal Physiology and Genetics of the Czech Academy of Sciences Rumburská 89 277 21 Liběchov Czech Republic

Institute of Animal Physiology Centre of Biosciences Slovak Academy of Sciences Šoltésovej 4 040 00 Košice Slovakia

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Int J Mol Sci. 2025 Feb 28;26(5):2171. doi: 10.3390/ijms26052171. PubMed

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Correction: Baran et al. Cleavage of Early Mouse Embryo with Damaged DNA. Int. J. Mol. Sci. 2022, 23, 3516

Checkpoint Kinase 1 Is a Key Signal Transducer of DNA Damage in the Early Mammalian Cleavage Embryo