Hypoxia Promotes Invasion of Endometrial Stromal Cells via Hypoxia-Inducible Factor 1α Upregulation-Mediated β-Catenin Activation in Endometriosis

Endometriosis is a common benign gynecological disease defined as the presence of endometrial tissue outside the uterine cavity. The aim of this study was to identify the molecular mechanism underlying hypoxia-induced increases in invasive ability of human endometrial stromal cells (HESCs). Herein, we show that the expression levels of hypoxia-inducible factor lα (HIF-1α) and β-catenin were greater in ectopic endometriotic tissue compared with eutopic tissue from controls. Exposure of eutopic endometrial stromal cells under hypoxic conditions or treated with desferrioxamine (DFO, chemical hypoxia) resulted in a time-dependent increase in β-catenin expression and its dephosphorylation. Hypoxia/HIF-1α also activated the β-catenin/T-cell factor (TCF) signaling pathway and the expression of target genes, vascular endothelial growth factor and matrix metalloproteinase 9, and knockdown of HIF-1α or β-catenin abrogated hypoxia-induced increases in HESC invasiveness. These results suggest that HIF-1α interacting with β-catenin/TCF signaling pathway, which is activated by hypoxia, may provide new insights into the etiology of endometriosis. Similar content being viewed by others

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