Uterine endothelial cell proliferation before and after embryo implantation in rats

Angiogenesis occurs rarely in normal adult tissues. The female reproductive tract, however, provides several exceptions, including the endometrium during early pregnancy. The aim of this study was to quantify endothelial cell proliferation (a component of angiogenesis) in the rat endometrium at about the time of implantation, using immunohistochemistry with a double staining technique. Proliferating cells were stained using an antibody against proliferating cell nuclear antigen (PCNA; clone PC10), and endothelial cells were stained with a lectin from Griffonia simplicifolia. Results showed that the endothelial cell proliferative index in the endometrium rose significantly from approximately 1% on the first 2 days of pregnancy to 13% on day 3; and continued to rise to 28% on day 5. After embryo implantation, the endometrial endothelial cell proliferative index rose further to 71% on day 7 at embryo sites only; but significantly decreased to basal values at intersites. The endothelial cell proliferative indices in the myometrium and mesometrial triangle remained at basal values during the first 5 days, but increased to approximately 22% at embryo sites only by day 7. We conclude that in the rat: (1) endometrial angiogenesis may be occurring before embryo implantation; (2) endometrial endothelial and stromal cell proliferation occurs concomitantly, except on day 3 when endothelial cell proliferation begins in advance of other stromal cell proliferation; and (3) there are two separate mechanisms controlling uterine endothelial cell proliferation during early pregnancy. The first mechanism is maternally controlled and is apparent throughout the entire endometrium from day 3; and the second mechanism is apparent after implantation in the vicinity of the embryo.