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Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice

Nature Genetics volume 39, pages 966–968 (2007)Cite this article

Abstract

The spindle assembly checkpoint guards against chromosomal missegregation but does not induce arrest in oocytes that contain a few achiasmatic chromosomes (univalents). We followed the fate of univalents in oocytes during the first meiotic division, and although these preserved a meiotic kinetochore structure, they were also bi-oriented in a mitotic manner. The hybrid chromosomal configuration attained by univalents allows them to evade the spindle assembly checkpoint and contribute to aneuploidy in oocytes.

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Figure 1: Sycp3−/− oocytes with an abnormal chromosomal composition are not arrested at MI despite the activity of a functional SAC.
Figure 2: Univalents in Sycp3−/− oocytes are bi-oriented in a mitotic manner and evade the SAC.

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Acknowledgements

We are grateful to S. Sahlen for the introduction to the SKY technique, L. Ferguson for the help with the oocyte collection, G. Greggains for the support in data analysis and O. Shupliakov and N. Tomilin for the assistance in the electron microscopy field. This work was supported by grants from the Swedish Cancer Society, the Swedish Research Council, Karolinska Institutet and a grant from Birth Defects Foundation to M.H.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, S-171 77, Sweden

    Anna Kouznetsova & Christer Höög

  2. Newcastle Fertility Centre, Institute of Human Genetics and North East England Stem Cell Institute, Newcastle University, Bioscience Building, International Centre for Life, Newcastle upon Tyne, NE1 4EP, UK

    Lisa Lister & Mary Herbert

  3. Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska University Hospital, Solna, 171 76, Sweden

    Magnus Nordenskjöld

Authors
  1. Anna Kouznetsova
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  2. Lisa Lister
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  3. Magnus Nordenskjöld
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  4. Mary Herbert
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  5. Christer Höög
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Contributions

A.K. and C.H. designed the experiments and wrote the manuscript. M.N. provided support with the SKY methodology. L.L., A.K. and M.H. performed the live cell imaging experiments.

Corresponding author

Correspondence to Christer Höög.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4, Supplementary Methods (PDF 1773 kb)

Supplementary Video 1

Chromosome dynamics at the first meiotic division for a wild-type oocyte. (MOV 1021 kb)

Supplementary Video 2

Chromosome dynamics at the first meiotic division for an Sycp3−/− oocyte. (MOV 486 kb)

Supplementary Video 3

3D reconstruction of the kinetochore region of a centrally positioned univalent. (MOV 770 kb)

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Kouznetsova, A., Lister, L., Nordenskjöld, M. et al. Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice. Nat Genet 39, 966–968 (2007). https://doi.org/10.1038/ng2065

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