O-039 Fertilization: Mechanisms of pronuclear migration and genome unification

Abstract

Abstract Most early human embryos contain aneuploid cells. Aneuploidy often arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. I will present data showing how the parental genomes cluster with nucleoli in each pronucleus in human and bovine zygotes. Parental genome clustering is required for the reliable unification of the parental genomes after fertilization. During the migration of intact pronuclei, the parental genomes polarize toward each other in a process driven by centrosomes, dynein, microtubules, and nuclear pore complexes. The maternal and paternal chromosomes eventually cluster at the pronuclear interface, in close proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes upon nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei that are incompatible with healthy embryonic development. In summary, our data reveal why nucleolar clustering correlates with the formation of healthy euploid embryos. In addition, we used automated analysis of nucleolar trajectories and clustering. Our results support the use of nucleolar clustering as a parameter to identify zygotes with higher developmental potential.