EMBRYO-DERIVED PLATELET-ACTIVATING FACTOR MODULATES ENDOMETRIAL AND EDCIDUAL PRODUCTION OF ANGIOGENIC FACTORS DURING IMPLANTATION.

血小板活化因子(PAF)是一种强有力的脂质介质，参与了包括着床在内的许多生殖过程。PAF已经被证明是由人类胚胎产生的，这似乎是生存所必需的。然而，胚胎来源的PAF在着床中的确切作用尚未确定。为了探讨PAF在子宫内膜或蜕膜血管生成中的作用，我们评估了子宫内膜间质细胞(ESC)或蜕膜细胞(DC)产生的各种血管生成因子或抗血管生成因子。用氨甲酰-PAF类似物(C-PAF)刺激ESC和DC，测定培养上清液中三种血管生成因子的浓度。这种底物不会被代谢。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。采用酶联免疫吸附测定法。采用免疫印迹法检测C-PAF刺激后ESC和DC中TSP-1蛋白的表达。未受刺激的ESC结构性地分泌血管内皮生长因子、b-成纤维细胞生长因子和血管生成素。随着C-PAF加入量的增加，刺激的ESC和DC培养上清液中血管生成因子的水平也随之升高。C-PAF对DC的刺激作用是ESC的2~3倍。用PAF受体拮抗剂Y-24180和CV2086预先阻断C-PAF的上述效应。C-PAF对ESC和DC中TSP-1的产生无影响。提示蜕膜组织和发育中的胚胎分泌的PAF刺激胎儿-母体交界处血管生成因子的产生。这些因素在局部环境中的上调可能在妊娠早期的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 endometrial or decidual angiogenesis, we evaluated the production of various angiogenic factors or anti-angiogenic factors by endometrial stromal cells (ESC) or decidual cells (DC). We measured the concentrations of three angiogenic factors in the culture media of ESC 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 ESC and DC after stimulation with C-PAF using western blot analysis. The non-stimulated ESC constitutively secreted VEGF, b-FGF, and angiogenin. The levels of these angiogenic factors in the culture media of the stimulated ESC and DC rose in accordance with an increase in the amount of C-PAF added. The C-PAF-induced stimulation in DC was two or three times more potent than that in ESC. These C-PAF-induced effects were abolished following pretreatment with PAF receptor antagonists, Y-24180 and CV2086. C-PAF had no effect on TSP-1 production in ESC and DC. It is suggested that the PAF secreted by the decidual tissue and by the developing embryo stimulates 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.