Ontogeny of the VATER kidney in a rat model.
By exposing rat fetuses to adriamycin prenatally, a rat model of VATER association has been created. Absence of the fetal bladder is prominent and the kidneys show features of chronic obstruction with hydronephrosis/hydroureter, loss of parenchyma, fewer glomeruli, and less differentiation. The aim of this study was to elucidate this rat model, to determine exactly when the changes in the kidneys develop, hopefully thereby to expand our understanding of congenital obstructive uropathy. Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin on days 6-9 of gestation. The control group received saline. Fetuses were recovered on gestational days (GDs) 20, 19, 18, 17, 16, 15, 14, 12, and 10 (total, 120 control, 121 treated). Macroscopic features were determined. Serial sections were then taken and stained with hematoxylin and eosin. Comparisons were made under light microscopy. The metanephric kidney first became apparent at GD12. The development of the control and treated kidneys appeared similar till GD18. Beyond this day, the treated kidneys exhibited increasing degrees of distension of Bowman's capsule, ducts, and subsequently pelvis and ureter. There were fewer levels of glomeruli, which were also less differentiated. Less differentiation was also noted in the medulla, and with time this became thin in comparison to the control kidneys. By GD20, the renal pelvis was grossly dilated with a blunted papilla, and the renal parenchyma was thin. Prenatal exposure of rat fetuses to adriamycin results in kidneys that are chronically obstructed, as the majority of the fetuses show absence of the bladder. Absence of renal dysmorphology until GD18, when urine is first produced, suggests strongly that the effect of adriamycin on the kidney is indirect, via agenesis of the bladder and secondary to backpressure from early urine production. This is a unique, simple, and reliable model of fetal obstructive uropathy and will be very useful to facilitate further investigation into its pathophysiology and to explore new treatment options.
Temelcos
Catherine
C
F. Douglas Stephens Surgical Research Laboratory, Murdoch Children's Research Institute, Melbourne, Australia.
Hutson
John M
JM
D000014:Abnormalities, Drug-Induced / Q000196:embryology* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001743:Urinary Bladder / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology
D004317:Doxorubicin