Bivalent separation into univalents precedes age-related meiosis I errors in oocytes

Yogo Sakakibara, Shu Hashimoto, Yoshiharu Nakaoka, Anna Kouznetsova, Christer Höög and Tomoya S. Kitajima ()
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Yogo Sakakibara: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology
Shu Hashimoto: IVF Namba Clinic
Yoshiharu Nakaoka: IVF Namba Clinic
Anna Kouznetsova: Karolinska Institutet
Christer Höög: Karolinska Institutet
Tomoya S. Kitajima: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology

Nature Communications, 2015, vol. 6, issue 1, 1-8

Abstract: Abstract The frequency of chromosome segregation errors during meiosis I (MI) in oocytes increases with age. The two-hit model suggests that errors are caused by the combination of a first hit that creates susceptible crossover configurations and a second hit comprising an age-related reduction in chromosome cohesion. This model predicts an age-related increase in univalents, but direct evidence of this phenomenon as a major cause of segregation errors has been lacking. Here, we provide the first live analysis of single chromosomes undergoing segregation errors during MI in the oocytes of naturally aged mice. Chromosome tracking reveals that 80% of the errors are preceded by bivalent separation into univalents. The set of the univalents is biased towards balanced and unbalanced predivision of sister chromatids during MI. Moreover, we find univalents predisposed to predivision in human oocytes. This study defines premature bivalent separation into univalents as the primary defect responsible for age-related aneuploidy.

Date: 2015
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DOI: 10.1038/ncomms8550

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