Department of Physiology, School of Medicine, Wayne State University, Detroit, MI, USA.
Cell Cycle. 2012 Feb 15;11(4):740-8. doi: 10.4161/cc.11.4.19207.
High frequencies of chromosomal anomalies are reported in human and non-human primate in vitro-produced preimplantation embryos. It is unclear why certain embryos develop aneuploidies while others remain euploid. A differential susceptibility to aneuploidy is most likely a consequence of events that occur before oocyte collection. One hypothesis is that the relative transcript levels of cohesins, shugoshins and spindle assembly checkpoint genes are correlated with the occurrence of chromosomal anomalies. Transcript levels of these genes were quantified in individual oocytes that were either mature (group 1, low aneuploidy rate) or immature (group 2, high aneuploidy rate) at retrieval, utilizing TaqMan-based real-time PCR. The transcript level in each oocyte was categorized as absent, below the median or above the median in order to conduct comparisons. Statistically significant differences were observed between group 1 and group 2 for SGOL1 and BUB1. There were more oocytes with SGOL1 expression levels above the median in group 1, while oocytes lacking BUB1 were only observed in group 1. These findings suggest that higher SGOL1 levels in group 1 oocytes could better protect against a premature separation of sister chromatids than in embryos derived from group 2 oocytes. The absence of BUB1 transcripts in group 1 was frequently associated with reduced expression of either mitotic cohesins or shugoshins. We hypothesize that ablation of BUB1 could induce mitotic arrest in oocytes that fail to express a complete complement of cohesins and shugoshins, thereby reducing the number of developing aneuploid preimplantation embryos.
在人类和非人类灵长类动物的体外培养的胚胎中,报告了染色体异常的高频发生。目前尚不清楚为什么某些胚胎会出现非整倍体,而其他胚胎则保持整倍体。对非整倍体的易感性差异很可能是卵母细胞采集前发生的事件的结果。一种假设是,着丝粒蛋白、Shugoshin 和纺锤体组装检查点基因的相对转录水平与染色体异常的发生有关。利用 TaqMan 实时 PCR 定量分析了在采集时成熟(第 1 组,低非整倍体率)或不成熟(第 2 组,高非整倍体率)的个体卵母细胞中这些基因的转录水平。为了进行比较,将每个卵母细胞的转录水平分为缺失、低于中位数或高于中位数。SGOL1 和 BUB1 在第 1 组和第 2 组之间观察到统计学上的显著差异。第 1 组中具有 SGOL1 表达水平高于中位数的卵母细胞更多,而仅在第 1 组中观察到缺乏 BUB1 的卵母细胞。这些发现表明,第 1 组卵母细胞中 SGOL1 水平较高可能比第 2 组卵母细胞衍生的胚胎更好地保护姐妹染色单体过早分离。第 1 组中 BUB1 转录本的缺失通常与有丝分裂着丝粒蛋白或 Shugoshin 的表达减少有关。我们假设 BUB1 的缺失可能会诱导未能表达完整的着丝粒蛋白和 Shugoshin 复合物的卵母细胞发生有丝分裂停滞,从而减少发育中非整倍体的植入前胚胎数量。