Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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
_version_ 1784826499143041024
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
work_keys_str_mv AT currieceryse thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT fordemma thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT benhamwhytelucy thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT taylordeborahm thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT mihalasbettinap thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT erentmuriel thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT marstonadelel thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT hartshornegeraldinem thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT mcainshandrewd thefirstmitoticdivisionofhumanembryosishighlyerrorprone
AT currieceryse firstmitoticdivisionofhumanembryosishighlyerrorprone
AT fordemma firstmitoticdivisionofhumanembryosishighlyerrorprone
AT benhamwhytelucy firstmitoticdivisionofhumanembryosishighlyerrorprone
AT taylordeborahm firstmitoticdivisionofhumanembryosishighlyerrorprone
AT mihalasbettinap firstmitoticdivisionofhumanembryosishighlyerrorprone
AT erentmuriel firstmitoticdivisionofhumanembryosishighlyerrorprone
AT marstonadelel firstmitoticdivisionofhumanembryosishighlyerrorprone
AT hartshornegeraldinem firstmitoticdivisionofhumanembryosishighlyerrorprone
AT mcainshandrewd firstmitoticdivisionofhumanembryosishighlyerrorprone