Mesh : Humans Spindle Apparatus / metabolism Mitosis Cell Nucleus / metabolism Zygote / cytology metabolism Embryo, Mammalian / cytology Microscopy, Confocal Centrosome / metabolism Embryonic Development / physiology Female

来  源:   DOI:10.1038/s41467-024-49815-8   PDF(Pubmed)

Abstract:
During human embryonic development, early cleavage-stage embryos are more susceptible to errors. Studies have shown that many problems occur during the first mitosis, such as direct cleavage, chromosome segregation errors, and multinucleation. However, the mechanisms whereby these errors occur during the first mitosis in human embryos remain unknown. To clarify this aspect, in the present study, we image discarded living human two-pronuclear stage zygotes using fluorescent labeling and confocal microscopy without microinjection of DNA or mRNA and investigate the association between spindle shape and nuclear abnormality during the first mitosis. We observe that the first mitotic spindles vary, and low-aspect-ratio-shaped spindles tend to lead to the formation of multiple nuclei at the 2-cell stage. Moreover, we observe defocusing poles in many of the first mitotic spindles, which are strongly associated with multinucleation. Additionally, we show that differences in the positions of the centrosomes cause spindle abnormality in the first mitosis. Furthermore, many multinuclei are modified to form mononuclei after the second mitosis because the occurrence of pole defocusing is firmly reduced. Our study will contribute markedly to research on the occurrence of mitotic errors during the early cleavage of human embryos.
摘要:
在人类胚胎发育过程中,早期卵裂期胚胎更容易出错.研究表明,在第一次有丝分裂过程中会出现许多问题,比如直接卵裂,染色体分离错误,和多核化。然而,在人类胚胎的第一次有丝分裂过程中发生这些错误的机制仍然未知。为了澄清这方面,在本研究中,我们使用荧光标记和共聚焦显微镜对丢弃的活人两核阶段受精卵进行成像,而不进行DNA或mRNA的显微注射,并研究纺锤体形状与第一次有丝分裂过程中核异常之间的关系。我们观察到第一个有丝分裂纺锤体变化,和低纵横比形状的纺锤体倾向于导致在2细胞阶段形成多个核。此外,我们观察到许多第一有丝分裂纺锤体的离焦极点,与多核化密切相关。此外,我们表明,中心体位置的差异会导致第一有丝分裂中的纺锤体异常。此外,许多多核在第二次有丝分裂后被修饰形成单核,因为极点散焦的发生明显减少。我们的研究将为人类胚胎早期卵裂过程中有丝分裂错误的发生做出显着贡献。
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