Fertilized eggs from primates have low developmental efficiency, with only about 50% reaching the blastocyst stage in vitro.
performed a long-term live-imaging analysis of spindle assembly in around 150 human and monkey embryos for 5 days.
The authors found that the second mitotic division is the most error-prone, with 2-cell blastomeres assembling multipolar spindles and missegregating chromosomes owing to stochastic centriole overduplication, which leads to early embryonic arrest.
Inhibition of PLK4, a kinase that drives centriole biogenesis and centrosome assembly, prevented centrosomal and spindle defects.
Understanding the mechanisms underlying inefficient pre-implantation development is crucial for developing novel strategies in assisted reproductive technology and for preventing silent miscarriage.
Fertilized eggs from primates have low developmental efficiency, with only about 50% reaching the blastocyst stage in vitro. To investigate the underlying cause, Li et al. performed a long-term live-imaging analysis of spindle assembly in around 150 human and monkey embryos for 5 days. The authors found that the second mitotic division is the most error-prone, with 2-cell blastomeres assembling multipolar spindles and missegregating chromosomes owing to stochastic centriole overduplication, which leads to early embryonic arrest. Inhibition of PLK4, a kinase that drives centriole biogenesis and centrosome assembly, prevented centrosomal and spindle defects. By contrast, late embryonic arrest involved the activation of the endoplasmic reticulum stress response, which could impair the expression of a subset of junctional and cell polarity proteins required for blastocyst formation. Understanding the mechanisms underlying inefficient pre-implantation development is crucial for developing novel strategies in assisted reproductive technology and for preventing silent miscarriage.
Original reference: Cell https://doi.org/10.1016/j.cell.2026.05.037 (2026)
