Bladder development following bladder outlet obstruction in fetal lambs: optimal timing of fetal therapy.
BACKGROUND
Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity.


METHODS
We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain.


RESULTS
The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent.


CONCLUSIONS
The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.
Department of Urology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
Kazuki
K
Kitajima
Takeshi
T
Aoba
Kevin C
KC
Pringle
Yasuji
Y
Seki
Jane
J
Zuccollo
Junki
J
Koike
Tatsuya
T
Chikaraishi
Hiroaki
H
Kitagawa
D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000648:ultrastructure; D005260:Female; D046128:Fetal Therapies; D005355:Fibrosis; D005865:Gestational Age; D006984:Hypertrophy; D008026:Ligation; D008297:Male; D009130:Muscle, Smooth / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D011312:Pressure; D012756:Sheep / Q000196:embryology; D013997:Time Factors; D014497:Urachus / Q000601:surgery; D014521:Urethra / Q000601:surgery; D001743:Urinary Bladder / Q000196:embryology* / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000196:embryology*