Secreted Protein, Acidic and Rich in Cysteine (SPARC) and Thrombospondin in the Developing Follicle and Corpus Luteum of the Rat

Abstract

In adult mammals, growth of new vasculature from extant blood vessels (angiogenesis) is rare in the absence of pathology. However, nonpathogenic angiogenesis occurs in the cycling ovary when the avascular postovulatory follicle transforms into a highly vascularized corpus luteum (CL). To improve our understanding of molecular mechanisms that regulate nonpathogenic vascular growth, we characterized the expression of two secreted matricellular proteins associated with angiogenesis, SPARC and thrombospondin (TSP), in postovulatory preluteal follicles and CL of hormone-primed immature rats. By indirect immunofluorescence with specific antibodies, we found SPARC in the cytoplasm of granulosa cells and thecal cells of preluteal follicles, in connective tissue cells of the ovarian interstitium, and in the oocyte nucleus. Administration of a luteinizing stimulus (chorionic gonadotropin) increased the expression of SPARC in granulosa cells. TSP was prominent in the basement membranes of growing follicles. Many cells in the early vascularizing CL expressed both SPARC and TSP. Neovascularization of CL was accompanied by expression of SPARC in nascent vessels and concentration of TSP in central avascular areas. In mature CL, steroidogenic luteal cells expressed both SPARC and TSP. Luteal cells of regressing CL retained SPARC to a variable degree but did not express TSP. The observed changes in expression of SPARC and TSP during development of the CL support distinct roles for these matricellular proteins in nonpathological morphogenesis and angiogenesis.