Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture

To investigate the basic pathophysiology of renal cystic maldevelopment, the production of renal cysts was studied in a newly developed murine metanephric organ culture system. In this isolated, nonvascularized system, the addition of hydrocortisone (1.4 X 10(-5) M) to completely characterized, serum-free growth medium produced striking tubular cystic abnormalities. As nephron obstruction did not occur in the nonperfused organ culture system in which neither glomerular filtration nor urine flow were present, the model experimentally isolated the roles of tubular cell metabolism and tubular wall extracellular matrix development in the production of cystic alterations. Analysis with the techniques of intact nephron microdissection and light and electron microscopy demonstrated that organ culture cysts developed in proximal tubules amid a normal background of organotypic tubular differentiation and glomerular epithelial development. Frank cystic development in the system was regularly preceded by ultrastructural alterations in and around the walls of differentiating proximal tubules. Such changes consisted of basolateral intercellular spreading which increased with progressive tubular dilation and irregular thickening and lamellation of tubular basal laminae. The ultrastructural features of the model suggest roles for hydrocortisone-induced alterations in both tubular transport processes and basal lamina structure in the experimental production of cysts. We conclude that the production of cystic changes in organ culture by hydrocortisone permits highly controlled study of the roles of altered tubular cell and basal lamina metabolism in the pathogenesis of cystic metanephric maldevelopment.