STIMULATION OF DEVELOPMENT IN-VITRO BY PLATELET-ACTIVATING-FACTOR RECEPTOR LIGANDS RELEASED BY MOUSE PREIMPLANTATION EMBRYOS

Previous reports have demonstrated that culture of mouse preimplantati on embryos at high density stimulates their rate of development. The m olecular basis of this phenomenon was investigated. Culture of embryos from the four-cell stage at high density in normal medium, or at low density either in embryo-conditioned medium or medium containing plate let-activating factor (PAF), significantly advanced the timing of comp action, initiation of cavitation and/or completion of zona hatching, a nd also increased the number of cells in blastocysts. In contrast, Lys o-PAF, an inactive metabolite of PAF, and Enantio-PAF, an enantiomer o f PAF, did not have a stimulatory effect at low embryo density, but di d not inhibit the stimulation of development at high embryo density. T he stimulatory effect of culture at high density was inhibited in the presence of either CV-3988 or SDZ 64-412, two structurally distinct co mpetitive PAF-receptor antagonists, while the development rate at low density was not affected. We conclude that an embryo-derived factor re lated to PAF is secreted by blastomeres during in vitro culture and ac ts in a receptor-mediated manner to stimulate the rate of development.