Angiogenesis in the corpus luteum

The ovarian corpus luteum plays a critical role in reproduction because it is the primary source of circulating progesterone. After ovulation, as the corpus luteum forms from the wall of the ruptured follicle, it grows and va scularizes extremely rapidly. In fact, the rates of tissue growth and angio genesis in the corpus luteum rival those of even the fastest growl ng tumor s. Thus, the corpus luteum provides an outstanding model for studying the f actors that regulate the angiogenic process, which is critical for normal t issue growth, development, and function. In agreement with data from other tissues, vascular endothelial growth factors (VEGF) seem to be a major angi ogenic factor responsible for vascularization of the developing corpus lute um. Recent data suggest that luteal expression of VEGF occurs primarily in specific perivascular cells, including arteriolar smooth muscle and capilla ry pericytes, and is regulated primarily by oxygen levels. In addition, soo n after ovulation, pericytes derived from the thecal compartment appear to be the first vascular cells to invade the developing luteal parenchyma. The granulosa-derived cells produce a factor that stimulates pericyte migratio n. Moreover, nitric oxide (NO), which is a potent vasodilator and can stimu late VEGF production and angiogenesis, is expressed in endothelial cells of luteal arterioles and capillaries, often in association with expression of VEGF by luteal perivascular cells. Thus, we have proposed a model for the initial process of luteal vascularization in which hypoxia plays a major ro le. In this model, which we believe will apply to other tissues as well, a paracrine loop exists between the vascular endothelial cells, which produce NO, and the peri-endothelial cells (vascular smooth muscle and pericytes), which produce VEGF, to ensure coordinate regulation of luteal vasodilation and angiogenesis.