Ontogeny of bladder agenesis in rats induced by adriamycin.

Abstract

To determine the anatomical steps leading to bladder agenesis in rats prenatally exposed as fetuses on gestational days (GD) 6-9 to adriamycin. Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin at 2 mg/kg (n = 28) on GD 6-9 (vaginal plug = day 0). The control group (n = 21) received saline. Fetuses were harvested on GD 10, 11, 12, 13, 14, 15 and 16. Serial paraffin sections were prepared from a minimum of 10 experimental and five control fetuses at each gestational age, and stained with either trichrome or haematoxylin and eosin, and examined by light microscopy. In the control group the urorectal septum first became visible and the mesonephric ducts apparently abutting the anterior cloaca on GD 12. The presumptive urinary bladder was clearly defined on GD 14. On GD 15, the common excretory ducts became incorporated into the newly formed urogenital sinus and the ureters opened into the bladder. In the treated animals, beginning on GD 11, the undivided cloaca was noticeably smaller and by GD 13-14, the vesical extension of the urogenital sinus was conspicuously absent. Instead, opposite ureters joined to drain directly into the proximal blind-ending urethra or the persistent distal urogenital sinus. Prenatal exposure of rat fetuses to adriamycin resulted in primary agenesis rather than secondary resorption of the bladder. The ontogeny showed that the mechanism underpinning bladder development is unique and is under the influence of factors that can be targeted by adriamycin. Further work will elucidate the unique nature of bladder organogenesis and should have important applications in future research into artificial bladders.