File:Age-related chromosome segregation errors during MI model.jpg

Premature bivalent separation into univalents precedes age-related chromosome segregation errors during MI.

Bivalents with weakened cohesion in aged oocytes undergo hyperstretching and separation into univalents by microtubule-mediated bipolar spindle forces. This bipolar forces in turn biorient the sister KTs of the univalents. The univalents are therefore strongly biased towards predivision of sister chromatids, including balanced predivision. After balanced predivision during MI, the chromatids undergo random segregation during MII.

Reference

PMID 26130582

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Nat Commun. 2015 Jul 1;6:7550. doi: 10.1038/ncomms8550. Bivalent separation into univalents precedes age-related meiosis I errors in oocytes. Sakakibara Y1, Hashimoto S2, Nakaoka Y2, Kouznetsova A3, Höög C3, Kitajima TS1. Author information 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. PMID: 26130582

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