Parental genome unification is highly error-prone in mammalian embryos.

Cell
T. CavazzaMelina Schuh

Abstract

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.

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Citations

Jun 23, 2021·Nature Communications·Sushil KhanalTomer Avidor-Reiss
Jul 14, 2021·Seminars in Cell & Developmental Biology·Julie Firmin, Jean-Léon Maître
May 31, 2021·Journal of Assisted Reproduction and Genetics·Giovanni CoticchioDavid F Albertini
Aug 28, 2021·International Journal of Molecular Sciences·Martin AngerMarketa Charousova
Sep 23, 2021·The Journal of Cell Biology·Isabell SchneiderJan Ellenberg
Jul 16, 2021·Journal of Molecular Cell Biology·Feifei Qi, Jun Zhou
Nov 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Daniel AriadRajiv C McCoy

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