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胚泡阶段经历发育停滞，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滞育，要么表现为与代谢应激有关的兼性滞育，要么表现为专性滞育，作为每一次妊娠的特征。本研究的长期目标是确定胚胎滞育的特征和调控。我们最近有了一个新的发现，一类被称为多胺的多阳离子子宫分泌物的缺乏是可逆性阻止胚胎发生的关键因素。此外，最近的文献表明，滞育的可能性存在于通常不会发生滞育的物种中。目前的建议是基于这样一个假设，即滞育是存在于几个分类群中的物种中的一种妊娠事件，具有共同的机制基础。在第一个目标中，将使用最先进的分子和细胞生物学工具，包括基因表达的全球分析，来研究多胺剥夺诱导滞育的机制。第二个目标是使用体内和体外模型相结合的方法来探索多胺的合成、相互转化和分泌的子宫机制。第三个目标是通过研究不经历滞育的物种来确定多胺对胚胎发生调控的普遍性。针对这些目标的实验将为滞育机制、早期胚胎发生和早期妊娠的母体-胚胎对话提供新的信息。我们已经证明，与多胺孵育可以提高胚胎的体外存活率，我们的新研究将集中在确定这一发现是否可以在非滞育物种上重复，非滞育物种是使用胚胎移植的重要经济物种。我们还预计，操纵胚胎的多胺供应将导致可逆的发育停滞，提供一种在没有冷冻破坏性影响的情况下保存胚胎的方法。因此，这项提议包括一项具有更大经济影响潜力的根本性调查。

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.