Transcriptomic profiling of human oocytes: association of meiotic aneuploidy and altered oocyte gene expression
Transcriptomic profiling of human oocytes: association of meiotic aneuploidy and altered oocyte gene expression
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DOI：
10.1093/molehr/gaq033
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发表时间：
2010-08-01
影响因子：
4
通讯作者：
Wells, D.
中科院分区：
文献类型：
--
作者：
Fragouli, E.;Bianchi, V.;Wells, D.
识别具有产生可存活胚胎的最大潜力的卵母细胞的能力将对辅助生殖治疗非常有益。影响卵母细胞的最重要的缺陷之一是非整倍性。非整倍体也与母亲年龄的增长密切相关，这是一种尚不清楚的现象。本研究结合了21个卵母细胞的全面细胞遗传学研究，并对其转录组进行了详细评估。从所有卵母细胞中去除第一极体，并使用比较基因组杂交评估非整倍性。初步的mRNA转录数据产生与使用微阵列的7个相应的卵母细胞（3个正常和4个非整倍体）。比较正常卵母细胞和非整倍体卵母细胞的结果，发现327个基因在转录水平上显示统计学显著差异（P < 0.05）。在7个非整倍体和7个正常卵母细胞中使用实时PCR进一步评估了这些基因中的96个。结果表明，非整倍体与影响基因子集的转录水平改变有关。还观察到mRNA转录本数量与年龄之间的联系。卵母细胞中不同的转录水平对细胞通路产生影响的可能性仍有待证实。然而，可能重要的是，一些突出显示的基因产生参与纺锤体组装和染色体排列的蛋白质。此外，几个基因的转录量改变产生细胞表面或排泄分子，并可能作为非侵入性卵母细胞非整倍性评估的目标。
The ability to identify oocytes with the greatest potential for producing a viable embryo would be of great benefit to assisted reproductive treatments. One of the most important defects affecting oocytes is aneuploidy. Aneuploidy is also closely related with advancing maternal age, a phenomenon not well understood. This study combined a comprehensive cytogenetic investigation of 21 oocytes with a detailed assessment of their transcriptome. The first polar body was removed from all oocytes and aneuploidy assessed using comparative genomic hybridization. Preliminary mRNA transcript data were produced with the use of microarrays for seven of the corresponding oocytes (three normal and four aneuploid). The results obtained for normal and aneuploid oocytes were compared and 327 genes were found to display statistically (P < 0.05) significant differences in transcript levels. Ninety-six of these genes were further assessed in seven aneuploid and seven normal oocytes using real-time PCR. The results indicated that aneuploidy is associated with altered transcript levels affecting a subset of genes. A link between mRNA transcript numbers and age was also observed. The possibility that different transcript levels in the oocyte have an impact on cellular pathways remains to be proven. However, it may be significant that some of the highlighted genes produce proteins involved in spindle assembly and chromosome alignment. Additionally, several genes with altered amounts of transcript produce cell surface or excretory molecules, and could potentially serve as targets for non-invasive oocyte aneuploidy assessment.