Bilateral megaureters in the Adriamycin rat model

Abstract

Congenital obstructive uropathy is associated with significant morbidity and mortality in the human neonate. The pathophysiology of congenital obstructive uropathy is poorly understood. There are very few experimental models of prenatal obstruction of the urinary tract, except in the fetal lamb or inbred rats. Prenatal exposure to Adriamycin in a rat model leads to a spectrum of malformations including urinary tract anomalies. We hypothesized that Adriamycin administration during a particular time frame could yield a high incidence of urinary tract anomalies and therefore designed this study to investigate the rates of urinary tract anomalies at different windows of Adriamycin injection in rat embryos. Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats at different times from days 6 to 10 of gestation. Control animals were given saline. Embryos recovered on gestational day 21 by cesarean section were examined for urinary tract anomalies, and malformations were noted. Sections were then processed for paraffin embedding, sectioned at 5 mum, and stained with hematoxylin and eosin for histological examination. Anomalies of the urinary tract occurred maximally following Adriamycin administration on days 7, 8, and 9 of gestation (91.6%) compared with 16% of controls. The most common urinary tract anomaly in the Adriamycin group was bilateral megaureters with a hypoplastic bladder (81%). Other anomalies included unilateral or bilateral ureterohydronephrosis with a normal-sized bladder, duplex kidney, and unilateral or bilateral renal agenesis. In conclusion, the critical embryologic window for the development of bilateral megaureters with a small bladder in the Adriamycin rat model occurs following Adriamycin administration on gestational days 7-9. This simple experimental model of bilateral megaureter may allow further research into the pathophysiology of this condition.