Transactions from the Thirty-Second Annual Scientific Meeting of the Society of Gynecologic Surgeons
Glycodelin mediates the increase in vascular endothelial growth factor in response to oxidative stress in the endometrium

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Objective

We hypothesized that glycodelin stimulates vascular endothelial growth factor (VEGF) expression in response to oxidative stress.

Study design

EM42 (human endometrial epithelial cell line) and primary endometrial epithelial cells were subjected to oxidative stress with minimally oxidized low density lipoprotein (mLDL). Cells were also incubated with no LDL (control) or native LDL (nLDL). Each condition was incubated with and without glycodelin antibody. Glycodelin and VEGF protein and messenger RNA (mRNA) levels were analyzed. Primary cells were cultured with glycodelin peptide to evaluate the effect on VEGF protein and mRNA.

Results

Glycodelin and VEGF protein and mRNA were higher for cells grown with mLDL (P < .05), while glycodelin antibody attenuated the increase in VEGF protein (P < .01). Glycodelin peptide increased VEGF mRNA and protein (P < .05).

Conclusion

Glycodelin may act as an autocrine factor within endometriotic implants to increase VEGF expression during oxidative stress.

Section snippets

Materials

Glycodelin peptide (H2N-YKKVLGEKTENPKKFK-COOH) was synthesized by the Microchemical Facility of Emory University, and an antibody to glycodelin peptide was generated in chicken as described.13 Chicken immunoglobulin G (IgG) and rabbit antichicken IgG conjugated with alkaline phosphatase were purchased from Sigma (St Louis, MO). VEGF enzyme-linked immunosorbent assay (ELISA) kit was purchased from R & D Systems, Inc (Minneapolis, MN). Micro-to-Midi Total RNA Purification System was purchased

Effect of oxidative stress on glycodelin protein

For mLDL-treated EM42 cells, glycodelin concentration was 10.25 ± 3.9 ng/mL, which was significantly greater than control (2.5 ± 0.41 ng/mL) (P < .05), and nLDL-treated cells (5.05 ± 0.99 ng/mL) (P < .05) (Figure 1). Glycodelin production by nLDL-treated cells was not significantly different from controls. For mLDL-treated primary epithelial cells, glycodelin concentration was 387% ± 84% higher than control (P < .05) (Figure 2). Glycodelin from cells treated with nLDL (167% ± 48% of control)

Comment

The pathogenesis of endometriosis remains an enigma and many clues to the disease lie within the peritoneal fluid. The PF of women with endometriosis contains numerous cytokines and growth factors that are significantly elevated or altered when compared with disease-free women.2, 12, 20 The PF of women with endometriosis also has been shown to contain minimally oxidized LDL.3, 12, 21

We have generated extensive evidence that suggests women with endometriosis have enhanced oxidative stress.12, 22

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    Support provided by NIH/NICHD 1PO1HD35276 awarded to S.P. and A.M. and NIH/NICHD K24HD01471-01 awarded to A.M.

    Presented at the Thirty-Second Annual Meeting of the Society of Gynecologic Surgeons, April 3 through 5, 2006, Tucson, AZ.

    The views expressed herein are those of the authors and do not necessarily reflect the views of the Veterans Administration or the US government.

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