[doi: 10.5505/2017ichc.OP-19]

Investigation Of Obstructive Uropathy For Histopathologic Changes And Apoptosis In Urinary System Of Adriamycin-Exposed Rat Fetuses

Sule Yalcin1, Işık Ünal2, Elif Kırlı1, Pergin Atilla2, Sevda Muftuoglu2, Ibrahim Karnak1
1Department of Paediatric Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey
2Department of Histology & Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey

The aim of this study is to analyse prenatal occurrence of bilateral megaureters with bladder hypoplasia by aid of adriamycin rat model, with investigation of histopathologic changes and apoptosis in urinary system.We suppose to provide additional data for pathophysiology of megaureter and obstructive uropathy association, with the goal of better understanding the correct diagnostic and therapeutic approach. Female Wistar rats were time-mated, and pregnancy was confirmed by positive vaginal smear next morning.Rats(n=30) were injected intraperitoneally with adriamycin and control rats (n=10) were injected with saline on 7, 8 and 9th days of gestation.Fetuses were recovered by cesarian section on the 21st day of gestation,examined for malformations and urinary tract were harvested from kidneys to urethra. Specimens were processed for paraffin embedding,sections were stained with H&E for histopathological evaluation,apoptosis were investigated with TUNNEL. Mann-Whitney-U test was used for statistical analysis.Fetuses in adriamycin group revealed bilateral megaureter, bladder hypoplasia/agenesis, with associated anomalies of renal agenesis, ureter agenesis, short tail in some of them whereas saline group had no associated anomaly.In histopathologic evaluation of saline group kidney, ureter and bladder were observed with their Subcapsular cortical nephrons and juxtamedullary nephrons.Beneath the capsule, a nephrogenic mesenchymal zone was found where new glomeruli in different stages of maturation were present.In adriamycin group,less mature smaller sized glomeruli were evaluated as a undeveloped glomerulus at subcapsullar region.However tubular structures cannot be differentiated as proximal or distal tubules.Juxtamedullary nephrons were almost completed but they were appeared with toxic effect of adriamisin having degenerative cells, detached podocytes &dilatations of capillary.Some glomerules of juxtamedullary nephrons had sloughed podocytes within the enlarged urinary space.Proximal tubule cells revealed eosinophilic cytoplasm,pyknotic nucleus, intracellular vacuolization.Distal tubules had similar degenerative cells.In medulla,collecting ducts appeared with small clustures of degenerative cells within the lumen close to the dilated vasa recta.Ureters and bladder were observed with apoptotic cells within their transitional epithelium and smooth muscle cells.The apoptotic index was calculated for renal cortex,medulla,epithelial-smooth muscle layers of ureter and bladder,for both groups.Apoptotic index was found to be significantly higher in adriamycin group,at layers of bladder epithelium (p:0.003),ureter epithelium-smooth muscle (p:0.04),but there was no significant difference in other parts.



Figure-1

In adriamycin group less mature glomeruli were found in the subcapsuler part of the renal cortex. Proximal tubule cells revealed eosinophilic cytoplasm.There are dilated capillaries between tubules. Kidney, H&E, X200 objective.


Figure-2

In adriamycin group apoptotic cells within the epithelium of the urinary bladder. Urinary bladder, TUNEL-Hematoxylin, X630 objective.