Embryonic diapause

胚胎滞育是一种重要的进化策略，其中一些哺乳动物物种的胚胎在囊胚阶段经历发育停滞，随后被重新激活以植入子宫。 已知有100多个物种在妊娠期间表现出滞育，或者是与代谢应激相关的兼性滞育，或者是专性滞育，作为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，子宫分泌物中缺乏一类聚阳离子，称为多胺，是胚胎发生可逆性停滞的关键因素。 此外，最近的文献表明，滞育的可能性存在于通常不会发生的物种中。目前的建议是基于这样的假设，即滞育，一个妊娠事件存在于物种跨越几个类群，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，包括全球基因表达分析进行研究。第二个目标是探索子宫机制的合成，相互转换和分泌的多胺使用在体内和体外模型相结合。第三个目标是通过调查不经历滞育的物种来确定多胺调节胚胎发生的普遍性。 解决这些目标的实验将提供新的信息滞育的机制，早期胚胎发生和早期妊娠的母胚对话。 我们已经表明，与多胺孵育增加胚胎在体外的存活率，我们的新研究将集中在确定这一发现是否可以重演在非滞育，经济上重要的物种，胚胎移植。 我们还预计，操纵多胺的可用性胚胎将诱导可逆的发展停滞，提供了一种手段，胚胎保存没有冷冻的破坏性影响。 因此，该提案包括一项具有更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.