Abstract
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.
Highlights
Development of the early embryo in mammals is initiated by the fertilization of an oocyte by sperm [1]
Our results showed that Checkpoint kinase 2 (CHK2) accumulated near chromosomes after nuclear envelope breakdown (NEBD)
We investigated the potential functions of CHK2 during early embryonic development in mice
Summary
Development of the early embryo in mammals is initiated by the fertilization of an oocyte by sperm [1]. The mammalian oocyte completes second meiosis to form a zygote. The zygote undergoes the first cleavage to generate two cells under maternal regulation [2]. The embryonic genome is activated, and the embryo undergoes continuous cleavage to develop into a 4-cell embryo, 8cell embryo, morula and blastocyst. The embryo differentiates into the trophoblast ectoderm (TE) and inner cell mass (ICM) during the blastocyst stage [3]. Errors during this process lead to embryonic lethality and implantation failure
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