School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
Biol Reprod. 2013 Feb 7;88(2):31. doi: 10.1095/biolreprod.112.104786. Print 2013 Feb.
It is becoming clear that reduced chromosome cohesion is an important factor in the rise of maternal age-related aneuploidy. This reduction in cohesion has been observed both in human and mouse oocytes, and it can be measured directly by an increase with respect to maternal age in interkinetochore (iKT) distance between a sister chromatid pair. We have observed variations in iKT distance even in oocytes from young mice and wondered if such differences may predispose those oocytes displaying the greatest iKT distances to be becoming aneuploid. Therefore, we used two methods, one pharmacological (Aurora kinase inhibitor) and one genetic (Fzr1 knockout), to raise aneuploidy rates in oocytes from young mice (age, 1-3 mo) and to examine if those oocytes that were aneuploid had greater iKT distances. We observed that for both Aurora kinase inhibition and Fzr1 knockout, iKT distances were significantly greater in those oocytes that became aneuploid compared to those that remained euploid. Based on these results, we propose that individual oocytes undergo loss in chromosomal cohesion at different rates and that the greater this loss, the greater the risk for becoming aneuploid.
很明显，染色体凝聚的减少是导致母体年龄相关非整倍体增加的一个重要因素。这种凝聚的减少在人类和小鼠卵母细胞中都有观察到，可以通过姐妹染色单体对之间的动粒间（iKT）距离相对于母体年龄的增加来直接测量。我们甚至在年轻小鼠的卵母细胞中观察到 iKT 距离的变化，想知道如果这些差异可能使那些显示最大 iKT 距离的卵母细胞容易成为非整倍体。因此，我们使用了两种方法，一种是药理学的（极光激酶抑制剂），另一种是遗传学的（Fzr1 敲除），来提高年轻小鼠（1-3 月龄）卵母细胞的非整倍体率，并检查那些成为非整倍体的卵母细胞是否具有更大的 iKT 距离。我们观察到，对于极光激酶抑制和 Fzr1 敲除，与保持整倍体的卵母细胞相比，成为非整倍体的卵母细胞的 iKT 距离明显更大。基于这些结果，我们提出，个体卵母细胞以不同的速度经历染色体凝聚的丧失，而这种丧失越大，成为非整倍体的风险就越大。
