Endometrial microvascular growth in normal and dysfunctional states

As a tissue that exhibits rapid cyclical growth and shedding throughout the reproductive life of the female? human endometrium provides a good model f or the study of normal physiological angiogenesis. The objective of this pa per is to summarize recent data on endometrial vascular growth, present new data on regional variability in endothelial cell proliferation within the endometrium, and interpret this information in light of current knowledge o f the mechanisms by which angiogenesis occurs, Conventional angiogenesis no rmally involves a series of steps which include endothelial cell activation , breakdown of the basement membrane, migration and proliferation of the en dothelial cell, fusion of sprouts, and tube formation. Other mechanisms by which angiogenesis occurs include intussusception and vessel elongation. Us ing immunohistochemical techniques we have shown repeatedly that levels of endothelial cell proliferation within human endometrium do not show any con sistent pattern across the different stages of the menstrual cycle, which i s unexpected since significant vascular growth must occur during the prolif erative phase, when the endometrium increases in thickness by up to 4-fold. There are two possible explanations for this; either there is no obligator y link between endometrial endothelial cell proliferation and new vessel fo rmation, or there is significant variation in endothelial cell proliferatio n within different regions of the same uterus, Multiple samples from hyster ectomy specimens subsequently demonstrated that the variability is due to r eal differences between individuals, as well as showing that the endothelia l cell proliferation index is significantly elevated in functionalis compar ed with basalis, During these studies we observed that endothelial cell pro liferation nearly always appeared inside existing endometrial vessels, rath er than be associated with structures that could be identified as vascular sprouts, To explore further whether sprout formation occurs during endometr ial angiogenesis, we investigated the immunohistochemical distribution of i ntegrin alpha(v)beta(3) on endometrial endothelial cells, As for endothelia l cell proliferation, integrin alpha(v)beta(3) immunostaining was seen only on endothelial cells that appeared within existing blood vessels. The resu lts from these studies have major implications for our understanding of the mechanisms that control endometrial angiogenesis. The lack of correlation between menstrual cycle stage and endothelial cell proliferation index, or endothelial cell expression of integrin alpha(v)beta(3), suggests that vasc ular growth is not under the overall control of oestrogen and progesterone.