Obstruction of the male reproductive tract can occur for several reasons, e.g. infection, trauma, congenital defects, and vasectomy. The most common cause of male tract obstruction is vasectomy. Obstruction can theoretically have effects either proximal to or distal to the obstruction site. Most Studies of the effects of obstruction have been on the tract proximal to the obstruction (testis and epididymis) and have focused on the testis because of its important spermatogenic and steroidogenic functions. Studies of the epididymal response to obstruction have been fewer, and none have studied the in vivo capacity of the epididymal epithelium to carry out complex, but quantitiatable cell tasks while under the influence of the obstruction. Neither has it been determined whether cell functions altered under the influence of obstruction return to normal after surgical relief of obstruction. Such information is important to our understanding of the male infertility which persists after the clinical reversal of duct obstruction, whether from vasectomy or other causes. In this application we proposed to use the rat model to determine the influence of duct obstruction on epididymal protein synthesis and luminal secretion in vivo, and to determine whether detected changes are eliminated by surgical reconstruction of a patent duct. Studies of the effects of duct obstruction distal to the site of obstruction are few, but residual concerns about the connection between vasectomy and prostatic cancer make it important to carefully determine the effects of ductal obstruction on the prostate. We propose to study the effects of vas deferens obstruction on the adult and study the effects of vas deferens obstruction on the adult and prepubertal prostate by measuring general parameters such as prostatic wt and total protein and DNA content, and by assessing the ability of the prostate to synthesize proteins and to secrete proteins into the glandular lumen in vivo. Changes detected after ductal obstruction will open opportunity to further studies into the mechanism of such changes.

Project Start
1999-07-01
Project End
2000-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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
Thornhill, B A; Forbes, M S; Marcinko, E S et al. (2007) Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction. Kidney Int 72:1103-12
Turner, Terry T; Johnston, Daniel S; Finger, Joshua N et al. (2007) Differential gene expression among the proximal segments of the rat epididymis is lost after efferent duct ligation. Biol Reprod 77:165-71
Burt, Laura E; Forbes, Michael S; Thornhill, Barbara A et al. (2007) Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF. Am J Physiol Renal Physiol 292:F168-74

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