Zielinska Agata P, Holubcova Zuzana, Blayney Martyn, Elder Kay, Schuh Melina
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Bourn Hall Clinic, Cambridge, United Kingdom.
Elife. 2015 Dec 15;4:e11389. doi: 10.7554/eLife.11389.
Aneuploidy in human eggs is the leading cause of pregnancy loss and Down's syndrome. Aneuploid eggs result from chromosome segregation errors when an egg develops from a progenitor cell, called an oocyte. The mechanisms that lead to an increase in aneuploidy with advanced maternal age are largely unclear. Here, we show that many sister kinetochores in human oocytes are separated and do not behave as a single functional unit during the first meiotic division. Having separated sister kinetochores allowed bivalents to rotate by 90 degrees on the spindle and increased the risk of merotelic kinetochore-microtubule attachments. Advanced maternal age led to an increase in sister kinetochore separation, rotated bivalents and merotelic attachments. Chromosome arm cohesion was weakened, and the fraction of bivalents that precociously dissociated into univalents was increased. Together, our data reveal multiple age-related changes in chromosome architecture that could explain why oocyte aneuploidy increases with advanced maternal age.
人类卵子中的非整倍体是妊娠丢失和唐氏综合征的主要原因。当卵子从称为卵母细胞的祖细胞发育而来时，非整倍体卵子是由染色体分离错误导致的。导致随着母亲年龄增长非整倍体增加的机制在很大程度上尚不清楚。在这里，我们表明，人类卵母细胞中的许多姐妹动粒在第一次减数分裂期间分离，并且不作为单个功能单元起作用。姐妹动粒分离使得二价体在纺锤体上旋转90度，并增加了着丝粒微管错向附着的风险。母亲年龄增长导致姐妹动粒分离增加、二价体旋转和着丝粒错向附着。染色体臂黏连减弱，早熟解离为单价体的二价体比例增加。总之，我们的数据揭示了染色体结构中与年龄相关的多种变化，这可以解释为什么卵母细胞非整倍体随着母亲年龄增长而增加。
