Delayed implantation and seasonal breeding

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Continuation of an active and successful research program to determine characteristics and regulation of a reproductive phenomenon known as obligate embryonic diapause (aka delayed implantation) is proposed. Diapause occurs when mammalian embryos undergo developmental arrest at the blastocyst stage, to be later reactivated and implanted for continuation of pregnancy. It is an evolutionary strategy that uncouples mating from gestation, allowing parturition at the optimal season for survival. Diapause is in the gestational program of several carnivore families including the weasels, bears and seals. It persists from a few weeks in spring breeding carnivores to several months in species that mate in the fall. The proposal is based on the hypothesis that embryonic diapause is regulated by factors secreted by the uterus, while embryo implantation is initiated and orchestrated by the activated embryo. The overall objective is to determine the cellular mechanisms of the developmental arrest in embryonic diapause and to explore the embryo-uterine dialog that reactivates the embryo and induces implantation into the uterus. The model employed is the ranch mink. The first specific objective is to exploit results of our recent gene discovery investigation to determine mechanisms by which the uterus and embryo regulate entry and exit of the embryo from diapause. Embryos will be collected at the morula stage and entry into diapause chronicled in vitro, as will exit from diapause in embryos collected in vivo, by probing for expression of cell signaling and cell cycle regulatory genes. The pattern of expression of factors secreted by the uterus and their capacity to reactivate embryos in vitro will be tested. The second specific objective is to investigate trophoblast as a regulator of local processes of implantation, and endometrial invasion. It will be addressed by examination of formation and regulation of the invasive component, the syncytial trophoblast and by investigation of morphological and gene expression events of uterine remodeling. New insight into diapause and implantation and information significant to understanding placental formation and embryo loss in other mammals will be gained from these novel experiments and approaches.