DEVELOPMENTAL ALTERATIONS IN THE FETAL LAMB BLADDER SUBJECTED TO PARTIAL URETHRAL OBSTRUCTION IN-UTERO

To identify the structural changes seen in the developing bladder subj ected to outflow obstruction, a fetal lamb model was developed. With t his 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 detrus or cellularity and innervation in the developing bladder. Partial uret hral obstruction was created in 9 fetal sheep (90 to 100 days gestatio n), 6 sham operated animals serving as controls. Fetuses were delivere d at term and sacrificed. Bladders were removed and weighed. Mucosa fr ee detrusor was assayed for DNA and choline acetyltransferase (ChAT) a ctivity, indices of cell number and cholinergic innervation, respectiv ely. In similar specimens of detrusor, cell ploidy and nuclear size we re determined by flow cytometry and nuclear morphometry, respectively. The results showed that partial urethral obstruction in utero resulte d in a significant increase in bladder weight (p < 0.05) and total det rusor DNA content (p < 0.01). With the increase in detrusor DNA conten t, there was a parallel increase in total detrusor ChAT activity. Thes e results suggest that early development of the bladder is altered bot h on a cellular level (increase in cellularity) and a neural level (in crease in cholinergic nerve density) under conditions of mechanical di stension.