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Expression profiles of cohesins shugoshins and spindle assembly checkpoint genes in rhesus macaque oocytes predict their susceptibility for aneuploidy during embryonic development

机译:猕猴卵母细胞中黏着蛋白寿神菌和纺锤体装配检查点基因的表达谱预测它们在胚胎发育过程中非整倍性的易感性

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摘要

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.
机译:在人类和非人类的灵长类动物体外产生的植入前胚胎中,染色体异常的发生率很高。目前尚不清楚为什么某些胚胎会产生非整倍性,而另一些仍保持整倍性。对非整倍性的敏感性差异很可能是卵母细胞收集之前发生的事件的结果。一种假设是粘着蛋白,shugoshins和纺锤体装配检查点基因的相对转录水平与染色体异常的发生有关。利用基于TaqMan的实时PCR,在检索时成熟(第1组,非整倍体率低)或未成熟(第2组,非整倍体率)的单个卵母细胞中,对这些基因的转录水平进行定量。为了进行比较,将每个卵母细胞中的转录物水平分类为不存在,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着差异。在第1组中,SGOL1表达水平高于中值的卵母细胞更多,而仅在第1组中观察到缺少BUB1的卵母细胞。这些发现表明,与胚胎相比,第1组卵母细胞中较高的SGOL1水平可以更好地防止姐妹染色单体的过早分离。来自第2组卵母细胞。第1组中BUB1转录物的缺失通常与有丝分裂粘附素或补胎蛋白的表达降低有关。我们假设,BUB1的消融可能会在卵母细胞中诱导有丝分裂停滞,而卵母细胞无法表达完整的粘着蛋白和补胎蛋白,从而减少发育中的非整倍体植入前胚胎的数量。

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