Objective: The aim of this study was to identify a theoretical support for the prevention of urethral fistula following hypospadias repair, by comparing the preputial wound healing process in Sprague-Dawley (SD) rats with and without hypospadias induced by flutamide. Methods: Fifteen pregnant SD rats were randomly divided into three groups. These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11-17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology. The pregnant rats in the control groups were not administered flutamide. The pups from the control and experiment groups underwent an incision on the dorsal prepuce on postnatal day 25 and were sacrificed on postoperative days 3, 7, and 14 to collect penis samples. The penis morphology was examined in all groups. Subsequently, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3) expression levels in the different groups were measured at the indicated time points postoperatively using qRT-PCR and Western blot. Results: There was less regeneration of the subcutaneous tissue in hypospadias rats than in the sham-operated group (P < 0.05) on postoperative day 3. No differences were found in the regeneration of the subcutaneous tissue between these groups on postoperative days 7 or 14. Additionally, there were no differences in the epithelial cell regeneration between the control and the hypospadias groups at any postoperative timepoint. Moreover, the expression levels of TGF-β1, α-SMactin, and STAT3 were all significantly lower in hypospadias group than that in the sham-operated group (P < 0.05). Conclusion: The results from the present work suggest that preputial wound healing is retarded in rats with hypospadias induced by flutamide and that this retardation might result from multi-gene regulation.
Keywords: fistula; flutamide; hypospadias; prepuce.