Endometrial angiogenesis.
As a tissue that exhibits rapid cyclical growth and shedding throughout the reproductive life of the female, the human endometrium provides a good model for the study of normal physiological angiogenesis. This paper will review current information on the timing of angiogenesis during the menstrual cycle, the mechanisms involved in endometrial capillary formation, and current information on angiogenesis factors and inhibitors. Based on endothelial cell proliferation studies, the timing of angiogenesis during the menstrual cycle remains unclear. The major mechanism by which endometrial capillaries are formed is probably a mixture of elongation and intussusception, with minimal evidence currently available for sprouting. Numerous angiogenesis factors have been identified in endometrium, the most well studied of which is VEGF. However, to date there is no evidence supporting a relationship between the expression of any given angiogenic factor and the occurrence of angiogenesis in the endometrium. Very limited studies have been undertaken to date on endometrial angiogenesis inhibitors, although the precursors to many of the known proteolytic fragments which act as inhibitors exist in the endometrium. In conclusion, neither the timing of vascular growth during the menstrual cycle nor the mechanisms by which endometrial vessels are formed are currently understood, thus placing major limitations on our understanding of how angiogenesis promoters and inhibitors may act in human endometrium.