Testicular torsion occurs most commonly in pubertal and adolescent boys, and in the postnatal period of infancy. This lesion, important in pediatric urology, induces a significant reduction, even a cessation, of testicular blood flow and requires prompt treatment if complete atrophy of the testis is to be prevented. The seminiferous epithelium is extremely sensitive to ischemia, and even prompt surgical treatment for torsion rarely saves a biologically functioning testis. However, the pathophysiology of torsion remains largely unexplored. Important questions regarding the mechanisms of testicular injury during and after torsion remain unanswered. Also, the development of medical treatment regimens which might increase the chances of saving a biologically functioning testis after detorsion has received little attention. this application proposes to study the pathophysiology of testicular torsion, initially with an investigation of testicular blood flow in rats with torsion, graded for both degree and duration. Bilateral testicular blood flow will be examined both during torsion and at various time intervals (hrs - wks) after torsion repair. These data will be correlated with data on daily sperm production and intratesticular testosterone concentrations to determine if there are associations between these three factors. Additionally, the effects of graded testicular torsion on ipsilateral Leydig cell function will be examined. In other organs studied, tissue ischemia is typically followed by reperfusion injury due to an increase in oxygen radical formation int he reperfused tissue. This leads to subsequent lipid peroxidation of cell and mitochondrial membranes, and to cell death. In this application, we will investigate the effects of testicular torsion on oxygen radical formation in the testis and the mechanism by which such formation occurs. Also, we propose to study the effects of oxygen radical scavengers on post-torsion testicular oxygen radical concentrations and to determine the effect of scavengers on functional salvage of the torted testis. Thus, this application proposes studies of basic mechanisms of testicular pathophysiology, as well as potential treatments for the rescue of the torted testis.

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University of Virginia
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Forbes, Michael S; Thornhill, Barbara A; Minor, Jordan J et al. (2012) Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis. Am J Physiol Renal Physiol 303:F120-9
Yoo, Kee Hwan; Thornhill, Barbara A; Forbes, Michael S et al. (2010) Inducible nitric oxide synthase modulates hydronephrosis following partial or complete unilateral ureteral obstruction in the neonatal mouse. Am J Physiol Renal Physiol 298:F62-71
Lysiak, Jeffrey J; Kavoussi, Parviz K; Ellati, Riyad T et al. (2010) Angiogenesis therapy for the treatment of erectile dysfunction. J Sex Med 7:2554-63
Lysiak, Jeffrey J; Kirby, Jennifer L; Tremblay, Jacques J et al. (2009) Hypoxia-inducible factor-1alpha is constitutively expressed in murine Leydig cells and regulates 3beta-hydroxysteroid dehydrogenase type 1 promoter activity. J Androl 30:146-56
Turner, Terry T; Lysiak, Jeffrey J (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29:488-98
Turner, Terry T (2008) De Graaf's thread: the human epididymis. J Androl 29:237-50
Chevalier, Robert L (2008) Chronic partial ureteral obstruction and the developing kidney. Pediatr Radiol 38 Suppl 1:S35-40
Jelinsky, Scott A; Turner, Terry T; Bang, Hyun J et al. (2007) The rat epididymal transcriptome: comparison of segmental gene expression in the rat and mouse epididymides. Biol Reprod 76:561-70
Burt, Laura E; Forbes, Michael S; Thornhill, Barbara A et al. (2007) Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF. Am J Physiol Renal Physiol 292:F158-67
Chen, Christina O; Park, Matthew H; Forbes, Michael S et al. (2007) Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol Renal Physiol 292:F946-55

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