Embryonic and uterine factors in delayed implantation in rodents.

An hypothesis for delayed implantation and embryonic quiescence is proposed on the basis of adaptation of blastocysts to changes in their environment. The environmental factors considered consist of macromolecules and essential ions and metabolites such as Ca2+, Mg2+ and glucose. Macromolecules appear to induce an influx of these essential metabolites which is followed by metabolic enhancement in blastocysts in the absence of any of the essential factors, the initial stages of embryonic diapause follow. The prevention of influx of metabolites such as Ca2+ by specific inhibitors, D600 or papaverine, also prevents activation of blastocysts. Early cleavage stage embryos show little or no response to changes in environmental macromolecules which may explain why embryos usually enter into quiescence at the blastocyst stage when the environmental constraints on blastocyst development become very marked. This also coincides with termination of cleavage and initiation of cell growth in embryos. The increase in responsiveness of embryos is attributed to several inherent changes including cell surface and functional changes in the plasma membrane. The conditions for embryonic quiescence in vivo are not species specific. Trophoblastic vesicles without the inner cell mass can also enter into quiescence. Studies using the antibiotic, tunicamycin, which inhibits protein glycosylation and prevents trophoblast adhesion and giant cell outgrowths, suggest that the cell surface interactions may involve glycoproteins. Such interactions may be crucial for implantation as well as for maintaining embryos in diapause for prolonged periods of time. A short sojourn in diapause for certain blastocysts which do not normally develop to an advanced stage, appears to have a beneficial effect on subsequent development. The overall significance of this suggestion for other species showing obligatory diapause is unclear.