Glycodelin mediates vascular endothelial growth factor (VEGF) production during oxidative stress of endometrial epithelial cells

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The purpose of this study was to determine the relationship between glycodelin and vascular endothelial growth factor (VEGF) produced by endometrial epithelial cells while subjected to oxidative stress. We hypothesized that glycodelin, produced during oxidative stress, promotes VEGF expression in endometrial epithelial cells. In vitro study. Cultures of EM42 cells (human endometrial epithelial cell line) were grown at a concentration of 1 × 103/ml. The EM42 cells were subjected to oxidative stress in the form of minimally oxidized LDL (mLDL) and extensively oxidized LDL (oxLDL). Cells were grown for 24 hrs with media containing either no LDL, 20 μg/ml of native LDL (nLDL), 20 μg/ml of mLDL, or 20 μg/ml of oxLDL. Each condition was grown with and without 50 μg of glycodelin antibody. Cell culture supernatant was removed after 24 hrs and ELISA assays were performed for glycodelin and VEGF. Glycodelin concentrations were significantly higher in EM42 cells grown with nLDL (P<0.05), mLDL (P<0.01) and oxLDL (P<0.01) compared to controls. Maximal glycodelin concentration was from cells grown with mLDL and was significantly higher compared to cells grown with nLDL (P<0.05). Concentration of VEGF was significantly increased for EM42 cells treated with mLDL (P<0.01) and oxLDL (P<0.01) compared to controls. Maximal VEGF concentration was found from cells grown with mLDL, which was significantly higher compared to cells grown with oxLDL (P<0.05). The addition of glycodelin antibody resulted in a significant reduction in VEGF concentration for cells grown with mLDL (P<0.01) and oxLDL (P<0.05). Statistical analysis was performed by ANOVA followed by the t test using the Bonferroni correction for multiple comparisons. This study demonstrates that oxidative stress in the form of mLDL and oxLDL increases EM42 cell production of glycodelin and VEGF. These angiogenic proteins may contribute to ectopic endometrial cell neovascularization as a result of oxidative stress. In addition, this study demonstrates that VEGF regulation is at least partly mediated by the glycodelin produced by EM42 cells during oxidative stress.