Department of Genetics and Reproduction, Central European Institute of Technology, Veterinary Research Institute, Brno, Czech Republic.
Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic.
Reproduction. 2020 Nov;160(5):773-782. doi: 10.1530/REP-20-0086.
Aneuploidy is the most frequent single cause leading into the termination of early development in human and animal reproduction. Although the mouse is frequently used as a model organism for studying the aneuploidy, we have only incomplete information about the frequency of numerical chromosomal aberrations throughout development, usually limited to a particular stage or assumed from the occurrence of micronuclei. In our study, we systematically scored aneuploidy in in vivo mouse embryos, from zygotes up to 16-cell stage, using kinetochore counting assay. We show here that the frequency of aneuploidy per blastomere remains relatively similar from zygotes until 8-cell embryos and then increases in 16-cell embryos. Due to the accumulation of blastomeres, aneuploidy per embryo increases gradually during this developmental period. Our data also revealed that the aneuploidy from zygotes and 2-cell embryos does not propagate further into later developmental stages, suggesting that embryos suffering from aneuploidy are eliminated at this stage. Experiments with reconstituted live embryos revealed, that hyperploid blastomeres survive early development, although they exhibit slower cell cycle progression and suffer frequently from DNA fragmentation and cell cycle arrest.
非整倍体是导致人类和动物生殖早期发育终止的最常见单一原因。尽管小鼠常被用作研究非整倍体的模式生物，但我们对整个发育过程中染色体数目异常的频率仅有不完全的信息，通常仅限于特定阶段或假设微核的发生。在我们的研究中，我们使用着丝粒计数法系统地对体内小鼠胚胎进行了非整倍体评分，从受精卵到 8 细胞阶段。我们在这里表明，每个胚胎细胞的非整倍体频率从受精卵到 8 细胞胚胎相对保持相似，然后在 16 细胞胚胎中增加。由于胚胎细胞的积累，胚胎中非整倍体的数量在这段发育期间逐渐增加。我们的数据还表明，受精卵和 2 细胞胚胎的非整倍体不会进一步传播到后期发育阶段，这表明在这个阶段遭受非整倍体的胚胎被淘汰。用重构的活体胚胎进行的实验表明，多倍体胚胎细胞能够在早期发育中存活，尽管它们表现出较慢的细胞周期进程，并且经常遭受 DNA 片段化和细胞周期停滞。
