Developmental alterations in the fetal lamb bladder subjected to partial urethral obstruction in utero

To identify the structural changes seen in the developing bladder subjected to outflow obstruction, a fetal lamb model was developed. With this model, which attempts to reproduce conditions such as those found in posterior urethral valves, quantitative biochemical parameters were used to evaluate the effects of partial outflow obstruction on detrusor cellularity and innervation in the developing bladder. Partial urethral obstruction was created in 9 fetal sheep (90 to 100 days gestation), 6 sham operated animals serving as controls. Fetuses were delivered at term and sacrificed. Bladders were removed and weighed. Mucosa free detrusor was assayed for DNA and choline acetyltransferase (ChAT) activity, indices of cell number and cholinergic innervation, respectively. In similar specimens of detrusor, cell ploidy and nuclear size were determined by flow cytometry and nuclear morphometry, respectively. The results showed that partial urethral obstruction in utero resulted in a significant increase in bladder weight (p < 0.05) and total detrusor DNA content (p < 0.01). With the increase in detrusor DNA content, there was a parallel increase in total detrusor ChAT activity. These results suggest that early development of the bladder is altered both on a cellular level (increase in cellularity) and a neural level (increase in cholinergic nerve density) under conditions of mechanical distension.