Gradual changes during mouse preimplantation development could affect chromosome segregation fidelity.

After meiosis I, the fully differentiated oocyte is fertilized by the sperm and resumes meiosis II. The two divisions are very asymmetric to maintain a large cytoplasmic volume for storage. During both meiotic divisions, transcription is inactive and protein expression is translationally and post-translationally regulated. Because centrosomes are degraded during early oogenesis [26], multiple acentriolar MTOCs functionally replace them in meiotic spindle assembly [19,27]. Thereby, multipolar spindle intermediates preferentially form during prometaphase. Also the duration of the division phase in the cell cycle (M-phase) is very long: meiosis I can take up to 10 hours and meiosis II can be especially delayed due to a metaphase arrest until fertilization [28]. Therefore, the totipotent zygote undergoes the first mitosis under unusual conditions, and the described and depicted parameters only gradually change during the early divisions: in every cleavage, the cell size is halved, whereas the genomic content should remain constant [25]. Through stored and activated mRNA, the zygote is still entirely under maternal translational control [23]. Only from the two-cell stage onwards—when transcription of the embryonic genome becomes activated—maternal control gets replaced by embryonic control [29]. Fewer and fewer MTOCs organize the mitotic spindle until centrosomes form de novo at the blastocyst stage. Until then, spindle assembly passes through less marked multipolar organization [30,31]. Also, M-phase duration changes: after very lengthy and even halted meiosis, the zygotic mitosis is still prolonged (approximately 90 to 120 minutes) compared to somatic mitosis [32,33]. Thereafter, the duration decreases until it reaches the timing of a normal somatic cell mitosis. These gradual changes during preimplantation development might contribute to decreased chromosome segregation fidelity during cleavage divisions. MTOC, microtubule organizing center.