Lack of correlation between vascular endothelial growth factor production and endothelial cell proliferation in the human endometrium

The role of vascular endothelial growth factor (VEGF) in endometrial angiog enesis was examined by measuring its production in human endometrial tissue s from different stages of the menstrual cycle and relating these data to e ndothelial cell proliferation in the same tissues. Conditioned medium was c ollected from explant, and separated glandular epithelial and stromal cells cultured from 24 normal human endometrial biopsies and VEGF measured by en zyme-linked immunosorbent assay (ELISA). Immunohistochemistry was also used to assess VEGF and the percentage of proliferating microvessels in the sam ples. Wide variation in results between individual endometrial samples at e ach stage of the menstrual cycle was observed for all parameters measured. There was no significant difference in VEGF secretion by explant, glandular epithelial or stromal cell cultures across the menstrual cycle, or in the percentage of proliferating vessels. VEGF inmunostaining in the stroma was elevated during the early proliferative stage (P = 0.03). Epithelial cells secreted more VEGF than stromal cells (1.76 +/- 0.46 versus 0.46 +/- 0.06 n g per 10(5) cells; P = 0.002). There was no correlation between VEGF secret ed by cultured explants, epithelial or stromal cells, VEGF immunostaining a nd the proportion of proliferating microvessels. These results show that th e majority of endometrial VEGF is produced by glands, but neither total gla ndular nor stromal VEGF is correlated with endometrial endothelial cell pro liferation. There is still no clear understanding on the regulation of huma n endometrial angiogenesis.