Parental genome unification is highly error-prone in mammalian embryos

Most human embryos are aneuploid. Aneuploidy frequently 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. Here, we show that the parental genomes cluster with nucleoli in each pronucleus within human and bovine zygotes, and clustering is required for the reliable unification of the parental genomes after fertilization. During 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 direct proximity to each other, yet separated. Parental genome clustering ensures the rapid unification of the parental genomes on nuclear envelope breakdown. However, clustering often fails, leading to chromosome segregation errors and micronuclei, incompatible with healthy embryo development.

Files

json

DOI:10.1016/j.cell.2021.04.013

Code

Compute nuclear chromatin distribution in zygotes

SWHID:swh:1:dir:99b72c30ebb767297a70fa7296e748f77ed7232f

Reagents

Parental genome unification is highly error-prone in mammalian embryos

URL:https://www.addgene.org/browse/article/28216708/

Code

Reagents

Network