CYCLIC ANGIOGENESIS AND BLOOD-VESSEL REGRESSION IN THE OVARY - BLOOD-VESSEL REGRESSION DURING LUTEOLYSIS INVOLVES ENDOTHELIAL-CELL DETACHMENT AND VESSEL OCCLUSION

Angiogenesis occurs as a cyclically regulated process in the ovary and the uterus. After ovulation, there is massive sprouting of blood vess els in the growing corpus luteum (CL) during the first third of the ov arian cycle. During luteolysis and for several weeks thereafter, all n ewly formed vessels regress. Here we have systematically analyzed regr ession of blood vessels during luteolysis to identify mechanisms of bl ood vessel regression. Blood vessel counts are highest in the midcycle Ct and drop rapidly after the onset of luteolysis. After a rapid phas e of tissue dissociation, blood vessel regression proceeds slowly over several weeks in the residual CL. Endothelial cells in regressing ves sels acquire a distinctly rounded and condensed phenotype. Ultrastruct ural analysis of blood vessel regression processes in the cyclic CL su ggests two major mechanisms of blood vessel regression: a) detachment of rounded endothelial cells from their basement membrane, leaving are as devoid of covering endothelial cell monolayer, and b) contraction a nd occlusion of arterioles and small arteries with pronounced prolifer ation of smooth muscle cells. In situ detection of nucleosomal fragmen tation products demonstrates numerous apoptotic luteal cells, but only a few apoptotic endothelial cells in the regressing CL. Induction of apoptosis in cultured endothelial cell monolayers by RGD peptides demo nstrated that endothelial cells detach from their adhesive surface bef ore fully becoming positive for nucleosomal fragmentation products. Th ese data indicate that cyclic angiogenic processes in the ovary offer a suitable experimental system to analyze mechanisms of blood vessel g rowth and regression, and suggest that detachment of endothelial cells before apoptosis as well as contractive occlusion of blood Vessels ma y be critical determinants of blood vessel regression.