Polyamines Are Implicated in the Emergence of the Embryo from Obligate Diapause

Polyamine deprivation maintains embryos in embryonic diapause and induces a delay of the timing of embryo implantation; polyamines are essential to reactivation of embryo in obligate diapause. Embryonic diapause is a poorly understood phenomenon of reversible arrest of embryo development prior to implantation. In many carnivores, such as the mink (Neovison vison), obligate diapause characterizes each gestation. Embryo reactivation is controlled by the uterus by mechanisms that remain elusive. Because polyamines are essential regulators of cell proliferation and growth, it was hypothesized that they trigger embryo reactivation. To test this, mated mink females were treated with α-difluoromethylornithine, an inhibitor of ornithine decarboxylase 1, the rate-limiting enzyme in polyamine biosynthesis, or saline as a control during the first 5 d of reactivation. This treatment induced polyamine deprivation with the consequence of rearrest in embryo cell proliferation. A mink trophoblast cell line in vitro subjected to α-difluoromethylornithine treatment likewise displayed an arrest in cell proliferation, morphological changes, and intracellular translocation of ornithine decarboxylase 1 protein. The arrest in embryo development deferred implantation for a period consistent with the length of treatment. Successful implantation and parturition ensued. We conclude that polyamine deprivation brought about a reversible rearrest of embryo development, which returned the mink embryo to diapause and induced a second delay in embryo implantation. The results are the first demonstration of a factor essential to reactivation of embryos in obligate diapause.