Platelet-activating factor-mediated regulation of angiogenesis in the chorionic villi and the decidua.

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Platelet-activating factor(PAF), a potent lipid mediator, has been implicated in a number of reproductive processes, including implantation. PAF has been shown to be produced by human embryo, which appears to be a requisite for viability. However the precise role of embryo-derived PAF in implantation has yet to be established. To investigate the role of PAF in chorionic or decidual angiogenesis, we evaluated the production of various angiogenic factors or anti-angiogenic factors by trophoblast cells(TC) or decidual cells(DC). We measured the concentrations of three angiogenic factors in the culture media of TC and DC following stimulation with an analogue, carbamyl-PAF(C-PAF). This substrate is not metabolized. These three factors were vascular endothelial growth factor(VEGF), basic fibroblast growth factor(b-FGF) and angiogenin. Enzyme-linked immunosorbent assay was used. In addition, we evaluated the expression of thrombospondin(TSP)-1 protein in TC and DC after stimulation with C-PAF using western blot analysis. The levels of VEGF, b-FGF, and angiogenin in the culture media of the C-PAF-stimulated TC and DC rose as an increase in the amount of C-PAF added. These C-PAF-induced effects were abolished following pretreatment with PAF receptor antagonists, Y-24180 and CV2086. A PKC activator, TPA also stimulated these angiogenic factors, which was abolished by a PKC inhibitor, H-7. C-PAF had no effect on TSP-1 production in TC and DC. It is suggested that the PAF secreted by the decidual tissue and by the developing embryo stimulates via PKC the production of these angiogenic factors at the feto-maternal interface. The up-regulation of these factors in the local environment may be important in the angiogenesis during early stages of gestation.