Urinary diversion results in marked decreases in proliferation and apoptosis in fetal bladder

We sought to determine if bladder cycling is required for remodeling during fetal development.

For this study 5 fetal sheep bladders were harvested after 2 weeks of urinary diversion, initiated at approximately 90 days of gestation. Six unoperated sheep bladders of approximately 105 days of gestational age were used as controls. Dividing cells and cells undergoing apoptosis were quantified by using Ki-67 antibody and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay, respectively. In addition, expression of the antiapoptosis gene, Bcl2, and cell division control protein 42 were quantified by real-time polymerase chain reaction.

The thickness of bladder tissue layers is dramatically altered as a consequence of urinary diversion (defunctionalization). The percentage of Ki-67 and TUNEL positive cells in control bladders was 5.8% and 47.1%, respectively. However, in diverted bladders apoptosis and cell mitosis were significantly decreased with essentially 0% of Ki-67 and TUNEL positive cells per microscope field in the mucosa and detrusor muscle layers. In addition, relative mRNA expression of antiapoptotic gene Bcl2 was significantly lower in control than in diverted bladder tissue, while Cdc42 was significantly higher in the detrusor but not in the lamina propria.

Cell mitotic activity and coordinated cell death appear to be involved in growth and remodeling, which are activated by the mechanical input that occurs during bladder cycling. Fetal urinary diversion results in a repression of mitotic and apoptotic activity, limiting normal bladder growth and remodeling.