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The first mitotic division of human embryos is highly error prone
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Currie, Cerys E., Ford, Emma, Benham Whyte, Lucy, Taylor, Deborah M., Mihalas, Bettina P., Erent, Muriel, Marston, Adele L., Hartshorne, Geraldine M. and McAinsh, Andrew D. (2022) The first mitotic division of human embryos is highly error prone. Nature Communications, 13 (1). 6755. doi:10.1038/s41467-022-34294-6 ISSN 2041-1723.
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Official URL: https://doi.org/10.1038/s41467-022-34294-6
Abstract
Human beings are made of ~50 trillion cells which arise from serial mitotic divisions of a single cell - the fertilised egg. Remarkably, the early human embryo is often chromosomally abnormal, and many are mosaic, with the karyotype differing from one cell to another. Mosaicism presumably arises from chromosome segregation errors during the early mitotic divisions, although these events have never been visualised in living human embryos. Here, we establish live cell imaging of chromosome segregation using normally fertilised embryos from an egg-share-to-research programme, as well as embryos deselected during fertility treatment. We reveal that the first mitotic division has an extended prometaphase/metaphase and exhibits phenotypes that can cause nondisjunction. These included multipolar chromosome segregations and lagging chromosomes that lead to formation of micronuclei. Analysis of nuclear number and size provides evidence of equivalent phenotypes in 2-cell human embryos that gave rise to live births. Together this shows that errors in the first mitotic division can be tolerated in human embryos and uncovers cell biological events that contribute to preimplantation mosaicism.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Journal or Publication Title: | Nature Communications | ||||||
| Publisher: | Nature Publishing Group UK | ||||||
| ISSN: | 2041-1723 | ||||||
| Official Date: | 8 November 2022 | ||||||
| Dates: |
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| Volume: | 13 | ||||||
| Number: | 1 | ||||||
| Article Number: | 6755 | ||||||
| DOI: | 10.1038/s41467-022-34294-6 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 28 November 2022 | ||||||
| Date of first compliant Open Access: | 28 November 2022 | ||||||
| Related URLs: |
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