Embryonic diapause

胚胎滞育是一种重要的进化策略，某些哺乳动物的胚胎在囊胚阶段发育停止，随后被重新激活以植入子宫。已知有100多种物种在妊娠期间表现出滞育，要么是伴随代谢应激的兼性滞育，要么是专性滞育，这是每次妊娠的一个特征。本研究计划的长期目标是确定胚胎滞育的特征和调控。我们最近有了新的发现，子宫分泌的一类多阳离子，即多胺，是胚胎发生可逆性停止的关键因素。此外，最近的文献表明，在通常不发生滞育的物种中存在滞育的可能性。目前的建议是基于一个假设，即滞育，一个存在于几个分类群的物种的妊娠事件，有一个共同的机制基础。在第一个目标中，多胺剥夺诱导滞育的机制将使用最先进的分子和细胞生物学工具进行研究，包括基因表达的全局分析。第二个目标是利用体内和体外模型相结合的方法，探索子宫多胺合成、相互转化和分泌的机制。第三个目标是通过研究不经历滞育的物种来确定多胺调控胚胎发生的普遍性。针对这些目标的实验将提供有关滞育机制，早期胚胎发生和早期妊娠母胚对话的新信息。我们已经证明，用多胺孵育可以提高体外胚胎存活率，我们的新研究将集中在确定这一发现是否可以在非滞育、经济上重要的物种中重现，胚胎移植被采用。我们还期望操纵多胺对胚胎的可用性将诱导可逆的发育停止，为胚胎保存提供一种没有冷冻破坏性影响的手段。因此，这项建议包括一项具有较高经济影响潜力的基本调查。

Embryonic diapause is an important evolutionary strategy in which embryos in some species of mammals undergo developmental arrest at the blastocyst stage, to be later reactivated to implant into the uterus. More than 100 species are known to display diapause during gestation, either in its facultative form, associated with metabolic stress or in its obligate form, as a feature of every gestation. The long term objective of this research program is to determine the characteristics and regulation of embryonic diapause. We recently made the novel discovery that paucity of uterine secretions of a class of polycations, known as polyamines, are the key element in the reversible arrest of embryogenesis. Further, recent literature indicates that the potential for diapause exists in species where it does not normally occur. The current proposal is based on the hypothesis that diapause, a gestational event present in species across several taxa, has a common mechanistic basis. In the first objective, the mechanisms by which polyamine deprivation induces diapause will be investigated using state-of-the-art molecular and cell biology tools including global analysis of gene expression. The second goal is to explore the uterine mechanisms for the synthesis, interconversion and secretion of polyamines using a combination of in vivo and in vitro models. The third objective is to determine the universality of polyamine regulation of embryogenesis by investigating species that do not undergo diapause. The experiments addressing these objectives will provide novel information on the mechanisms of diapause, on early embryogenesis and on the maternal-embryo dialogue of early gestation. We have shown that incubation with polyamines increases embryo survival in vitro and our new studies will focus on determining if this finding can be recapitulated in non-diapause, economically important species where embryo transfer is employed. We also expect that manipulation of polyamine availability to embryos will induce reversible arrest in development, providing a means for embryo preservation without the devastating effects of freezing. Thus, this proposal comprises a fundamental investigation with an elevated potential for economic impact.