Bivalent separation into univalents precedes age-related meiosis I errors in oocytes.
Bivalent separation into univalents precedes age-related meiosis I errors in oocytes.
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DOI：
10.1038/ncomms8550
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发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Kitajima TS
中科院分区：
文献类型：
--
作者：
Sakakibara Y;Hashimoto S;Nakaoka Y;Kouznetsova A;Höög C;Kitajima TS
卵母细胞减数分裂I （MI）中染色体分离错误的频率随着年龄的增长而增加。两次命中模型表明，错误是由第一次命中造成易受影响的交叉构型和第二次命中造成与年龄相关的染色体内聚减少的组合引起的。该模型预测了单价与年龄相关的增加，但这种现象作为隔离错误的主要原因的直接证据一直缺乏。在这里，我们首次对自然衰老小鼠卵母细胞在MI过程中发生分离错误的单染色体进行了活体分析。染色体跟踪显示，80%的错误发生在二价分离成单价之前。在MI过程中，单价体偏向于姐妹染色单体的平衡和不平衡预分裂。此外，我们发现单价体在人类卵母细胞中倾向于预分裂。这项研究将过早的二价分离成一价定义为导致年龄相关非整倍体的主要缺陷。随着卵母细胞年龄的增长，减数分裂I期间染色体分离错误的频率增加。在这里，作者使用自然衰老小鼠卵母细胞的实时成像来提供直接证据，证明二价分离为单价是导致年龄相关非整倍体的主要缺陷。
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. As oocytes age the frequency of chromosome segregation errors during meiosis I increases. Here the authors use live imaging of oocytes from naturally aged mice to provide direct evidence that bivalent separation into univalents is the primary defect responsible for age-related aneuploidy.