Regulation of angiogenesis in the primate endometrium: vascular endothelial growth factor

Unlike other tissues, endometrial vessels are unique because their functions are primarily orchestrated under the influence of ovarian steroid hormones, estradiol and progesterone. Although there is controversy in the literature on the expression of steroid hormone receptors in endometrial endothelial and vascular smooth muscle cells, it is believed that the actions of estradiol and progesterone are primarily mediated by paracrine interactions between the vascular and other cells of the endometrium. However, the regulatory mechanisms and local factors involved in mediating these paracrine interactions are not fully understood. Numerous angiogenic factors have been identified and implicated in endometrial vascular development and differentiation, but their relative contribution in endometrial angiogenesis is unknown. This review primarily focuses on the current progress in understanding the roles of a prototypical angiogenic factor, the vascular endothelial growth factor (VEGF), in the primate endometrium. Regulation of VEGF and its receptors in the endometrium appears to be highly complex, regulated by both steroid hormones as well as local factors independent of steroid hormones. The zone-specific and the cell-type specific expression of VEGF and its receptors in the endometrium suggest that steroid hormones likely regulate their expression through local cell-specific regulatory factors, rather than through direct gene transcription. Because VEGF receptors are expressed in both endothelial and nonendothelial cells, VEGF may have a pleiotropic role in this tissue. Recent development of highly potent VEGF inhibitors provides an opportunity to study the roles of VEGF in the primate endometrium. It is imperative that future studies focus on understanding specific roles of VEGF using these inhibitors, which is critically needed for development of new therapeutic strategies for numerous endometrial vascular disorders.