title: Bivalent separation into univalents precedes age-related meiosis I errors in oocytes.
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.
authors.affiliation: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Yogo
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: IVF Namba Clinic, Osaka 550-0015, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: IVF Namba Clinic, Osaka 550-0015, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Nakaoka
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Kouznetsova
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
authors.affiliation: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Tomoya S
authors.initials: TS
authors.lastname: Kitajima
mesh_terms: D000367:Age Factors; D000782:Aneuploidy; D000818:Animals; D002842:Chromatids; D020090:Chromosome Segregation; D003434:Crossing Over, Genetic; D005260:Female; D006801:Humans; D018386:Kinetochores; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes; D059008:Time-Lapse Imaging