The unique transcriptome through day 3 of human preimplantation development
The unique transcriptome through day 3 of human preimplantation development
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DOI：
10.1093/hmg/ddh157
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发表时间：
2004-07-15
影响因子：
3.5
通讯作者：
Pera, RAR
中科院分区：
文献类型：
--
作者：
Dobson, AT;Raja, R;Pera, RAR
人类的成功发育取决于受精后的一连串事件。不幸的是，对人类这些关键事件的了解非常不完整。尽管每年在世界各地的不孕不育中心培养数十万人类胚胎，但绝大多数胚胎在培养或转移到子宫后未能发育。在这项研究中，我们试图用微阵列来表征个体正常胚胎在胚胎生命的前三天的基因表达的全球模式;然后我们用定量PCR比较了正常生长和生长停滞胚胎之间的基因表达。我们的研究结果记录了几个新的发现。首先，我们发现存在一种复杂的基因表达模式;大多数在受精后前三天转录调节的基因并没有像以前认为的那样上调，而是下调。其次，我们观察到，大多数在植入前发育过程中表现出差异表达的基因是未知的身份和/或功能。第三，我们表明，胚胎转录程序在受精后第3天就已经明确建立，即使是在2-，3-或4-细胞的胚胎中也是如此。这表明转录激活失败与大多数人类植入前胚胎丢失无关。最后，综合考虑，这些结果提供了人类植入前胚胎转录组的第一个全球性分析，并证明RNA可以从单个卵母细胞和胚胎中扩增，通过cDNA微阵列技术进行分析，从而为这些细胞类型以及其他小生物样品中的遗传调控的额外研究提供了证据。
Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the uterus. In this study, we sought to characterize global patterns of gene expression in individual, normal embryos during the first three days of embryonic life using microarrays; we then compared gene expression between normally growing and growth-arrested embryos using quantitative PCR. Our results documented several novel findings. First, we found that a complex pattern of gene expression exists; most genes that are transcriptionally modulated during the first three days following fertilization are not upregulated, as was previously thought, but are downregulated. Second, we observed that the majority of genes exhibiting differential expression during preimplantation development are of unknown identity and/or function. Third, we show that embryonic transcriptional programs are clearly established by day 3 following fertilization, even in embryos that arrested prematurely with 2-, 3- or 4-cells. This indicates that failure to activate transcription is not associated with the majority of human preimplantation embryo loss. Finally, taken together, these results provide the first global analysis of the human preimplantation embryo transcriptome, and demonstrate that RNA can be amplified from single oocytes and embryos for analysis by cDNA microarray technology, thus lending credence to additional studies of genetic regulation in these cell types, as well as in other small biological samples.