Regulation of angiogenic factors by hypoxia and female sex steroids in human endometrium

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The aim of this study is to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1), and the potential role of hypoxia-inducible factor-1 (HIF-1) in the endometrium. Hypoxia simultaneously induced expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 in a time-dependent manner. With regard to the interaction of estradiol and hypoxia, estradiol did not affect the regulation of VEGF under hypoxic conditions. Echinomycin, a small-molecule inhibitor of HIF-1 activity, inhibited hypoxia-induced VEGF production. Hypoxia simultaneously acts to increase VEGF via HIF-1. These results indicate a potential mechanism for the action of hypoxic conditions that could influence angiogenesis in the human endometrium.