Uterine endothelial cell proliferation before and after embryo implantation in rats

Abstract

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.

The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice

“…A similar pattern of endothelial cell proliferation has also been observed in pregnant rats (Goodger & Rogers 1993, Rabbani & Rogers 2001). This endothelial cell proliferation occurs concurrently with increasing plasma progesterone concentrations, which are also observed during early pregnancy in rodents (Finn & Martin 1969, McCormack & Greenwald 1974.…”

“…Gambino et al (2002) have shown that a form of branching angiogenesis (such as intussusception or sprouting) occurs in the human endometrium during the secretory phase of the menstrual cycle. In rats, endometrial endothelial cell proliferation increased significantly during early pregnancy when plasma progesterone concentrations are increasing prior to implantation (Goodger & Rogers 1993). It was also found that progesterone increased vascular density in ovariectomised mice while having little effect on vascular permeability (Ma et al 2001).…”

Myometrial cells induce angiogenesis and salvage damaged myocardium

“…4), the angiogenic effect was therefore produced by the biological activity of the implanted cells. 6 , arrows in C). D: after 8 days, implantation of MC 6 ϫ 10 6 produced significantly more arteriolar vessels, capillaries, and total blood vessels than implantation of MC 3 ϫ 10 6 .…”

“…To date, most research has focused on the effects of estrogen on endometrial angiogenesis, and, in general, estrogen is thought to stimulate new vessel growth. In contrast, few studies have been performed on the effects of progesterone on endometrial angiogenesis (6,19). Previous studies have produced conflicting results, either supporting a proangiogenic role (10) or an antiangiogenic role (24) for progesterone.…”

Abortifacient potential of methanolic extract of Anthocephalus cadamba stem bark in mice

“…It maintains uterine milieu for implantation and maturation of fertilized egg and prevents further egg release until the pregnancy has terminated (Goodger and Rogers, 1993). The decrease in progesterone level in the extract treated mice may result in impaired uterine milieu required for fetal development.…”