Angiogenesis Occurs by Vessel Elongation in Proliferative Phase Human Endometrium

Background: Angiogenesis occurs by at least three mechanisms: sprouting, intussusception and elongation. Studies to date have failed to identify the mechanisms or timing of endometrial angiogenesis during the menstrual cycle. The aim of this study was to determine if vessel elongation plays a role in human endometrial angiogenesis.

Methods: Forty-nine full thickness endometrial sections from 27 hysterectomy samples were immunostained for CD34 to identify blood vessels, and analysed using an interactive computerized stereological program. Based on counts from 9746 individual microscope fields, blood vessel length density (L(v)), branch point density (N(v)) and mean vessel length per branch point (L(v)/N(v)) were calculated for three endometrial zones during five phases of the menstrual cycle.

Results: There was an increase in L(v)/N(v) in the mid-late proliferative compared with early proliferative, early-mid secretory and late secretory phases of the menstrual cycle in the functionalis (mean +/- SEM: 174.5 +/- 20.1 versus 76.6 +/- 8.4, 118.6 +/- 9.4 and 104.2 +/- 4.1 microm respectively, P < 0.001) and between the mid-late proliferative and the menstrual phases in the basalis (158.0 +/- 18.2 versus 95.4 +/- 10.0 microm, P = 0.025). An increase in L(v) occurred in the subepithelial capillary plexus in the mid-late proliferative and early-mid secretory phases compared with the early proliferative phase (316.7 +/- 32.4 and 338.8 +/- 45.3 versus 178.5 +/- 8.9 mm/mm(3), P = 0.027).

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