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The First Mitotic Division of the Human Embryo is Highly Error-prone

Emma Ford, View ORCID ProfileCerys E. Currie, Deborah M. Taylor, Muriel Erent, View ORCID ProfileAdele L. Marston, View ORCID ProfileGeraldine M. Hartshorne, View ORCID ProfileAndrew D. McAinsh
doi: https://doi.org/10.1101/2020.07.17.208744
Emma Ford
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3Centre for Mechanochemical Cell Biology, University of Warwick, Coventry CV4 7AL, UK
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Cerys E. Currie
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3Centre for Mechanochemical Cell Biology, University of Warwick, Coventry CV4 7AL, UK
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Deborah M. Taylor
2University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
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Muriel Erent
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3Centre for Mechanochemical Cell Biology, University of Warwick, Coventry CV4 7AL, UK
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Adele L. Marston
4Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
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Geraldine M. Hartshorne
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
2University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
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  • For correspondence: a.d.mcainsh@warwick.ac.uk geraldine.hartshorne@warwick.ac.uk
Andrew D. McAinsh
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3Centre for Mechanochemical Cell Biology, University of Warwick, Coventry CV4 7AL, UK
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  • For correspondence: a.d.mcainsh@warwick.ac.uk geraldine.hartshorne@warwick.ac.uk
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Abstract

Aneuploidy in human embryos is surprisingly prevalent and increases drastically with maternal age, resulting in miscarriages, infertility and birth defects. Frequent errors during the meiotic divisions cause this aneuploidy, while age-independent errors during the first cleavage divisions of the embryo also contribute. However, the underlying mechanisms are poorly understood, largely because these events have never been visualised in living human embryos. Here, using cell-permeable DNA dyes, we film chromosome segregation during the first and second mitotic cleavage divisions in human embryos from women undergoing assisted reproduction following ovarian stimulation. We show that the first mitotic division takes several hours to complete and is highly variable. Timings of key mitotic events were, however, largely consistent with clinical videos of embryos that gave rise to live births. Multipolar divisions and lagging chromosomes during anaphase were frequent with no maternal age association. In contrast, the second mitosis was shorter and underwent mostly bipolar divisions with no detectable lagging chromosomes. We propose that the first mitotic division in humans is a unique and highly error-prone event, which contributes to fetal aneuploidies.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 17, 2020.
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The First Mitotic Division of the Human Embryo is Highly Error-prone
Emma Ford, Cerys E. Currie, Deborah M. Taylor, Muriel Erent, Adele L. Marston, Geraldine M. Hartshorne, Andrew D. McAinsh
bioRxiv 2020.07.17.208744; doi: https://doi.org/10.1101/2020.07.17.208744
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The First Mitotic Division of the Human Embryo is Highly Error-prone
Emma Ford, Cerys E. Currie, Deborah M. Taylor, Muriel Erent, Adele L. Marston, Geraldine M. Hartshorne, Andrew D. McAinsh
bioRxiv 2020.07.17.208744; doi: https://doi.org/10.1101/2020.07.17.208744

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