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The first mitotic division of human embryos is highly error prone
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 fro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643329/ https://www.ncbi.nlm.nih.gov/pubmed/36347869 http://dx.doi.org/10.1038/s41467-022-34294-6 |
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author | Currie, Cerys E. Ford, Emma Benham Whyte, Lucy Taylor, Deborah M. Mihalas, Bettina P. Erent, Muriel Marston, Adele L. Hartshorne, Geraldine M. McAinsh, Andrew D. |
author_facet | Currie, Cerys E. Ford, Emma Benham Whyte, Lucy Taylor, Deborah M. Mihalas, Bettina P. Erent, Muriel Marston, Adele L. Hartshorne, Geraldine M. McAinsh, Andrew D. |
author_sort | Currie, Cerys E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9643329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96433292022-11-15 The first mitotic division of human embryos is highly error prone Currie, Cerys E. Ford, Emma Benham Whyte, Lucy Taylor, Deborah M. Mihalas, Bettina P. Erent, Muriel Marston, Adele L. Hartshorne, Geraldine M. McAinsh, Andrew D. Nat Commun Article 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. Nature Publishing Group UK 2022-11-08 /pmc/articles/PMC9643329/ /pubmed/36347869 http://dx.doi.org/10.1038/s41467-022-34294-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Currie, Cerys E. Ford, Emma Benham Whyte, Lucy Taylor, Deborah M. Mihalas, Bettina P. Erent, Muriel Marston, Adele L. Hartshorne, Geraldine M. McAinsh, Andrew D. The first mitotic division of human embryos is highly error prone |
title | The first mitotic division of human embryos is highly error prone |
title_full | The first mitotic division of human embryos is highly error prone |
title_fullStr | The first mitotic division of human embryos is highly error prone |
title_full_unstemmed | The first mitotic division of human embryos is highly error prone |
title_short | The first mitotic division of human embryos is highly error prone |
title_sort | first mitotic division of human embryos is highly error prone |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643329/ https://www.ncbi.nlm.nih.gov/pubmed/36347869 http://dx.doi.org/10.1038/s41467-022-34294-6 |
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