Expression and regulation of vascular endothelial growth factor in a firsttrimester trophoblast cell

Embryo implantation and development are critically dependent upon the spati al and temporal regulation of angiogenesis and localized vascular permeabil ity. A key mediator of these effects is the endothelial cell mitogen vascul ar endothelial growth factor (VEGF). VEGF has been shown to promote endomet rial vascular permeability, fetal vasculogenesis and placental, fetal and m aternal angiogenesis. However, the mechanism through which this regulation occurs in the placenta is poorly understood. This study was conducted to de termine if the pro-angiogenic cytokines, TNF-alpha and TGF-beta 1, affect V EGF expression in human first trimester trophoblasts. Culture of a first tr imester trophoblast cell line (HTR-8/SVneo), in the presence of either TNF- alpha or TGF-beta 1, resulted in the expression of significant levels of VE GF in culture. The trophoblast cell line also showed a time-dependent and a dose-dependent increase in VEGF mRNA levels when cultured in the presence of either TNF-alpha or TGF-beta 1. These results suggest that both TNF-alph a and TGF-beta 1 may regulate the production of VEGF in early gestational t rophoblasts and may therefore serve to modulate placental vascular permeabi lity and angiogenesis that are necessary for embryo implantation and placen tation. (C) 2000 Harcourt Publishers Ltd.