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

血小板活化因子（PAF）是一种有效的脂质介质，参与了包括着床在内的许多生殖过程。PAF已被证明是由人类胚胎产生的，这似乎是生存的必要条件。然而，胚胎来源的PAF在着床中的确切作用尚未确定。为了研究PAF在绒毛膜或蜕膜血管生成中的作用，我们评估了滋养细胞（TC）或蜕膜细胞（DC）产生各种血管生成因子或抗血管生成因子的情况。我们用类似物卡巴霉素- paf （C-PAF）刺激后，测量了TC和DC培养基中三种血管生成因子的浓度。这种底物不被代谢。这三种因子分别是血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（b-FGF）和血管生成素。采用酶联免疫吸附法。此外，我们利用western blot分析了C-PAF刺激后TC和DC中血小板反应蛋白(TSP)-1蛋白的表达。C-PAF刺激的TC和DC培养基中VEGF、b-FGF和血管生成素水平随着C-PAF添加量的增加而升高。在用PAF受体拮抗剂Y-24180和CV2086预处理后，这些c -PAF诱导的效应被消除。作为PKC激活剂，TPA也能刺激这些血管生成因子，而PKC抑制剂H-7可以消除这些因子。C-PAF对TC和DC中TSP-1的产生没有影响。这表明，由蜕膜组织和发育中的胚胎分泌的PAF通过PKC刺激这些血管生成因子在胎母界面的产生。这些因子在局部环境中的上调可能在妊娠早期血管生成中起重要作用。

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.