Embryonic diapause

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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.