Hyperplasia in the rabbit bladder urothelium following partial outlet obstruction. Autoradiographic evidence

Abstract

Previous experiments have shown that adult male rabbits subjected to partial outlet obstruction or overdistension and acutely labeled, 24 h later, in vivo or in vitro with 3H-Thymidine(3H-TdR) show high levels of incorporated radioactivity in bladder epithelium when they are visualized with autoradiography. To test the hypothesis that such labeling represents the onset of a wave of proliferation (that is, true hyperplasia), we injected 3H-TdR subcutaneously in two normal and three partially obstructed New Zealand White male rabbits on each of days One, Two or Three following obstruction. Bladders were excised on the seventh day(D) following obstruction or the sixth day after injection of normals. Under these conditions, cells labeled with 3H-TdR had the opportunity to proliferate, after labelling, for 6(OneD and Normals), 5(TwoD) or 4(ThreeD) days respectively. After processing tissues for autoradiography, normal bladders showed only trace levels of labeling. Animals exposed to 3H-TdR one day after obstruction, when large numbers of basal cells of the urothelium are known to incorporate 3HTdR (i.e., synthesize DNA), showed labeling in most layers of the urothelium seven days after injection, but levels of labeling in bladders injected TwoD or ThreeD were lower than those injected OneD after obstruction. The smaller numbers of urothelial cells labeled by 3H-TdR in TwoD bladders were found in clusters where one or two alternate or adjacent layers of cells were labeled. Obstructed animals injected ThreeD after surgery showed even less labeling. This evidence clearly supports the hypothesis that DNA synthesis that occurs in the urothelium within 24 h after obstruction is followed by proliferation, because by the seventh day, labeling can be found at all levels of the urothelium. The decline of labeling in TwoD and ThreeD animals suggests that the proliferative stimulus probably operates only during the first 24 h after insult. The data suggest that a substantial fraction of the urothelium enters one or more rounds of proliferation following obstruction and support the contention that hyperplasia does occur.

Temporal diabetes- and diuresis-induced remodeling of the urinary bladder in the rat

“…Autoradiography of overdistended bladders showed significant and substantial labeling that was confined to the urothelial basal cells (34). The proliferating urothelium might produce some factors that can modulate the proliferation of detrusor muscle cells (24,25).…”

Deletion of one SERCA2 allele confers protection against bladder wall hypertrophy in a murine model of partial bladder outlet obstruction

“…Several studies have looked at [H 3 ]thymidine incorporation into the bladder wall using either short-term in vivo (24 -48 h) or in vitro methods (23,24). Given the problems associated with in vivo use of radioisotopes for prolonged periods, there is a paucity of data looking at DNA synthesis in the bladder wall over a prolonged course of pBOO.…”

Inverse expression of uroplakins and inducible nitric oxide synthase in the urothelium of patients with bladder outlet obstruction

“…In humans, studies of the bladder wall as a consequence of BOO have focused mainly on the modifications of its muscle cells, connective tissue and innervation [2,3]. The effects of BOO on the urothelium have been analysed only in animal models, where it was proposed that overdistension associated with BOO might compromise the blood– urine barrier and induce urothelial hyperplasia [4,5].…”