Endocrine Gland-Derived Vascular Endothelial Growth Factor Is Expressed in Human Peri-implantation Endometrium, But Not in Endometrial Carcinoma

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is a newly identified angiogenic and permeability-enhancing factor, predominantly expressed in steroidogenic tissues. Recently, we found that EG-VEGF is also expressed in the normal peri-implantation endometrial samples from patients of reproductive ages (80%). Immunohistochemistry analysis showed that EG-VEGF is predominantly expressed in the glandular epithelial cells and its expression is dynamic during the menstrual cycle with a peak expression at the mid-luteal phase. We also found that EG-VEGF transcripts are up-regulated in all the peri-implantation endometrial samples from the patients after the ovulating dose of human chorionic gonadotropin in gonadotropin-stimulated cycles and patients receiving hormone replacement therapy. In in vitro endometrial cell culture, EG-VEGF mRNA was detected in endometrial cells only in the presence of steroids, suggesting that EG-VEGF expression is highly dependent on the steroid hormones. Subsequent expression analyses on the EG-VEGF receptors showed that hPK-R1 and hPK-R2 are differentially expressed in human endometrium, but show no significant correlation with the hormonal treatments. On the other hand, EG-VEGF transcript was rarely detected in the endometrial samples from the postmenopausal patients and patients with endometrial carcinoma. It may imply that EG-VEGF may only play a role in vascular function of peri-implantation endometrium, but is unlikely to be associated with the etiology of endometrial cancer development.