Parental genome unification is highly erroneous in mammalian embryos

Abstract

AbstractThe vast majority of human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but the origin of this remains elusive. Using bovine embryos as a model for human embryos, we identify an error-prone mechanism of parental genome unification which often results in aneuploidy. Surprisingly, genome unification initiates hours before breakdown of the two pronuclei that encapsulate the parental genomes. While still within intact pronuclei, the parental genomes polarize towards each other, in a process driven by centrosomes, dynein, and microtubules. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in direct proximity to each other. Parental genome clustering often fails however, leading to massive chromosome segregation errors, incompatible with healthy embryo development. Nucleoli, which associate with chromatin, also cluster at the pronuclear interface in human zygotes. Defects in nucleolar clustering correlate with failure in human embryo development, suggesting a conserved mechanism.