Dual Causes of Early Human Embryonic Developmental Arrest: Insights and Perspectives at The Subcellular Scale
- VernacularTitle:人类早期胚胎发育停滞双重成因的发现及亚细胞尺度展望
- Author:
Ya-Nan LÜ
1
;
Yu-Ting GUO
1
Author Information
- Publication Type:Journal Article
- Keywords: human pre-implantation embryo; developmental arrest; live-cell light-sheet microscopy; structured illumination microscopy; organelle interactions
- From: Progress in Biochemistry and Biophysics 2026;53(10):2846-2850
- CountryChina
- Language:Chinese
- Abstract: In human assisted reproductive technology (ART), embryos experience an extremely high rate of developmental arrest (over 50%) during the 5-day developmental window prior to blastocyst formation, which constitutes a major bottleneck limiting clinical pregnancy rates. A recent paper published in Cell titled “Two distinct causes contribute to the low efficiency of human pre-implantation development” reveals the two independent causes underlying this phenomenon. Utilizing a custom-developed high-throughput dual-view live-cell light-sheet microscope, the research team achieved the first continuous live-cell imaging of human and non-human primate embryos with high spatiotemporal resolution for up to 120 h. The study discovered that embryos are highly prone to errors during the second mitosis. Multipolar spindle assembly, triggered by centriole overduplication, leads to chromosome segregation errors and micronuclei formation, which subsequently induces early developmental arrest (prior to the 8-cell stage). Conversely, late developmental arrest (on day 4) is primarily driven by the endoplasmic reticulum (ER) stress response. Furthermore, the study demonstrated that transient treatment with a PLK4 inhibitor (centrinone) can effectively prevent spindle defects at the 2-cell stage. This research not only reshapes our understanding of the developmental dynamics of human pre-implantation embryos but also provides new insights into the mechanisms underlying human pre-implantation developmental arrest and offers valuable references for future studies on assisted reproduction and potential intervention strategies.
