Evidence for a role of capillary pericytes in vascular growth of the developing ovine corpus luteum

Because of rapid growth followed by spontaneous regression, the ovarian cor pus luteum (CL) is an excellent model to study angiogenesis in vivo. To eva luate the expression of vascular endothelial growth factor (VEGF) protein d uring luteal development, ovaries were collected from FSH-stimulated ewes t hroughout the estrous cycle. VEGF was immunolocalized in tissue sections by using an affinity-purified antibody. VEGF protein localized exclusively to the thecal layer of preovulatory follicles, while the granulosa was devoid of staining. Associated with the periovulatory period was intense expressi on of VEGF by thecal cells at the basement membrane and subsequent invasion of the granulosa layers by these VEGF-positive cells immediately after ovu lation. The early CL showed staining for VEGF in thecal-derived compartment s, and strong staining for VEGF was also seen in cells within the granulosa -derived parenchymal lobules. Dual immunohistochemical localization of VEGF and smooth muscle cell alpha -actin indicated that the VEGF-positive cells were capillary pericytes or vascular smooth muscle cells. In another exper iment, we quantified proliferation of endothelial cells and pericytes throu ghout luteal development. Pericytes represented a large proportion of the p roliferating cells during the early luteal phase and then decreased dramati cally. Perivascular cells, therefore, may play a critical role in angiogene sis that occurs during transformation of the follicle into the highly vascu lar CL of the sheep. As angiogenesis occurs only at the level of capillarie s, and pericytes are integral members of these microvessels, regulation of pericytes may provide a novel mechanism for regulating luteal growth and ti ssue growth in general.