Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA, 91125, USA.
Nat Commun. 2020 Jun 11;11(1):2958. doi: 10.1038/s41467-020-16796-3.
The high incidence of aneuploidy in the embryo is considered the principal cause for low human fecundity. However, the prevalence of aneuploidy dramatically declines as pregnancy progresses, with the steepest drop occurring as the embryo completes implantation. Despite the fact that the plasticity of the embryo in dealing with aneuploidy is fundamental to normal development, the mechanisms responsible for eliminating aneuploid cells are unclear. Here, using a mouse model of chromosome mosaicism, we show that aneuploid cells are preferentially eliminated from the embryonic lineage in a p53-dependent process involving both autophagy and apoptosis before, during and after implantation. Moreover, we show that diploid cells in mosaic embryos undertake compensatory proliferation during the implantation stages to confer embryonic viability. Together, our results indicate a close link between aneuploidy, autophagy, and apoptosis to refine the embryonic cell population and ensure only chromosomally fit cells proceed through development of the fetus.
胚胎中染色体非整倍体的高发被认为是人类生育力低下的主要原因。然而，随着妊娠的进展，非整倍体的发生率显著下降，在胚胎完成着床时下降幅度最大。尽管胚胎在应对非整倍体方面的可塑性对于正常发育至关重要，但负责消除非整倍体细胞的机制尚不清楚。在这里，我们使用染色体嵌合体的小鼠模型表明，在 p53 依赖性过程中，非整倍体细胞在胚胎谱系中被优先消除，该过程涉及自噬和凋亡，发生在着床前、着床时和着床后。此外，我们还表明，嵌合体胚胎中的二倍体细胞在着床阶段进行代偿性增殖，以赋予胚胎活力。总之，我们的研究结果表明，非整倍体、自噬和凋亡之间存在密切联系，以优化胚胎细胞群体，并确保只有染色体正常的细胞才能继续发育成胎儿。
