Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation
Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation
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DOI：
10.1073/pnas.0402597101
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发表时间：
2004-07-13
影响因子：
11.1
通讯作者：
Dey, SK
中科院分区：
文献类型：
--
作者：
Hamatani, T;Daikoku, T;Dey, SK
延迟着床(胚胎滞育)发生在胚泡阶段的胚胎达到暂停生命的状态时。在此期间，囊胚的生长非常缓慢，细胞分裂很少或没有分裂。七个不同目的近100只哺乳动物经历了延迟着床，但指导这一过程的潜在分子机制在很大程度上仍不清楚。在小鼠中，在植入前切除卵巢妊娠第4天的卵巢雌激素分泌会启动胚泡休眠，通过持续的黄体酮治疗，这种休眠通常持续1-2周，尽管胚泡存活率随着时间的推移而下降。雌激素注射能迅速激活胚泡，并将其植入孕激素刺激的子宫。使用这个模型，我们在这里表明，在被检查的20,000个基因中，只有229个在休眠和激活的囊胚之间有差异表达。改变基因的主要功能类别包括细胞周期、细胞信号和能量代谢途径，尤其强调了肝素结合的表皮生长因子样信号在胚泡-子宫着床串扰中的重要性。这些结果提供了证据，证明了囊胚的两种不同的生理状态--休眠和激活--在全球范围内是可以区分的，并强调了特定的分子途径在这些过程中的重要性。这项研究已经确定了候选基因，这些候选基因为深入分析它们的功能提供了机会，并为研究它们与囊胚休眠和激活的相关性提供了机会，在许多其他物种中，由于囊胚的可用性非常有限，无法或不可能对这些物种进行微阵列分析。
Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular mechanisms that direct this process remain largely unknown. In mice, ovariectomy before preimplantation ovarian estrogen secretion on day 4 of pregnancy initiates blastocyst dormancy, which normally lasts for 1-2 weeks by continued progesterone treatment, although blastocyst survival decreases with time. An estrogen injection rapidly activates blastocysts and initiates their implantation in the progesterone-primed uterus. Using this model, here we show that among -20,000 genes examined, only 229 are differentially expressed between dormant and activated blastocysts. The major functional categories of altered genes include the cell cycle, cell signaling, and energy metabolic pathways, particularly highlighting the importance of heparin-binding epidermal growth factor-like signaling in blastocyst- uterine crosstalk in implantation. The results provide evidence that the two different physiological states of the blastocyst, dormancy and activation, are molecularly distinguishable in a global perspective and underscore the importance of specific molecular pathways in these processes. This study has identified candidate genes that provide a scope for in-depth analysis of their functions and an opportunity for examining their relevance to blastocyst dormancy and activation in numerous other species for which microarray analysis is not available or possible due to very limited availability of blastocysts.