These data are the first evidence that vessel elongation is a major angiogenic mechanism in mid-late proliferative phase human endometrium.

Expression of angiogenic and lymphangiogenic factors by tumours may in¯uence the route of metastatic spread.

Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides.

The role of vascular endothelial growth factor (VEGF) in endometrial angiogenesis was examined by measuring its production in human endometrial tissues from different stages of the menstrual cycle and relating these data to endothelial cell proliferation in the same tissues. Conditioned medium was collected from explant, and separated glandular epithelial and stromal cells cultured from 24 normal human endometrial biopsies and VEGF measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was also used to assess VEGF and the percentage of proliferating microvessels in the samples. Wide variation in results between individual endometrial samples at each 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 immunostaining 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 ng per 10(5) cells; P = 0.002). There was no correlation between VEGF secreted by cultured explants, epithelial or stromal cells, VEGF immunostaining and the proportion of proliferating microvessels. These results show that the majority of endometrial VEGF is produced by glands, but neither total glandular nor stromal VEGF is correlated with endometrial endothelial cell proliferation. There is still no clear understanding on the regulation of human endometrial angiogenesis.