Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada; Department of Obstetrics and Gynaecology, University of Montréal, Montreal, QC H3T 1J4, Canada.
Curr Biol. 2017 Apr 3;27(7):1040-1047. doi: 10.1016/j.cub.2017.02.025.
Chromosome segregation errors in mammalian oocytes compromise development and are particularly prevalent in older females, but the aging-related cellular changes that promote segregation errors remain unclear [1, 2]. Aging causes a loss of meiotic chromosome cohesion, which can explain premature disjunction of sister chromatids [3-7], but why intact sister pairs should missegregate in meiosis-I (termed non-disjunction) remains unknown. Here, we show that oocytes from naturally aged mice exhibit substantially altered spindle microtubule dynamics, resulting in transiently multipolar spindles that predispose the oocytes to kinetochore-microtubule attachment defects and missegregation of intact sister chromatid pairs. Using classical micromanipulation approaches, including reciprocally transferring nuclei between young and aged oocytes, we show that altered microtubule dynamics are not attributable to age-related chromatin changes. We therefore report that altered microtubule dynamics is a novel primary lesion contributing to age-related oocyte segregation errors. We propose that, whereas cohesion loss can explain premature sister separation, classical non-disjunction is instead explained by altered microtubule dynamics, leading to aberrant spindle assembly.
哺乳动物卵母细胞中的染色体分离错误会影响胚胎发育，这种错误在老年女性中尤为常见，但导致这种错误的与衰老相关的细胞变化仍不清楚[1,2]。衰老会导致减数分裂染色体的黏合丧失，这可以解释姐妹染色单体的过早分离[3-7]，但为什么完整的姐妹对在减数分裂 I 中会发生错误分离（称为非分离）仍不清楚。在这里，我们发现自然衰老的小鼠卵母细胞的纺锤体微管动力学发生了显著改变，导致暂时的多极纺锤体，使卵母细胞易于发生动粒-微管附着缺陷和完整姐妹染色单体对的错误分离。我们使用经典的微操作方法，包括在年轻和衰老的卵母细胞之间相互转移核，表明微管动力学的改变不是由于与年龄相关的染色质变化引起的。因此，我们报告称，微管动力学的改变是导致与年龄相关的卵母细胞分离错误的一种新的原发性病变。我们提出，虽然黏合丧失可以解释姐妹提前分离，但经典的非分离则是由微管动力学的改变引起的，导致纺锤体组装异常。
