Acquired and congenital obstruction of the vas deferens, ureter and renal vasculature, lead to alterations in reproductive and kidney function. This renewal for an O'Brian urology Research Center is focused on the cellular and molecular mechanisms underlying neonatal or pre-pubertal obstruction of the testis, epididymidis, and kidney. Four projects by established senior investigators are proposed. Project 1 investigates the altered phenotype of renal tubular epithelial cells (RTE) after neonatal ureteral obstruction. Deranged cellular polarity, apoptosis and crosstalk between RTE and interstitial fibroblasts will be examined in a ureteral and single nephron obstruction models offering insight into pediatric hydronephrotic disorders. Project 2 investigates the regulatory mechanisms and genomic events leading to the development of obstructed renal vasculature, especially with regard to the role of angiotensin in preserving normal renal vascular morphology. Phenotypic changes, vascular remodeling, and the lineage of cells participating in vessel growth in angiotensin deficient mice will be investigated. Project 3 studies the effect of vasal obstruction on epithelial function both proximal to (epididymis) and distal to (prostate) the site of obstruction. Cellular biochemistry and synthetic events will be studies. Reversibility of changes in protein synthesis and luminal secretion following relief of obstruction will be studied in both epididymis and prostate. These data will provide insight into persistent infertility after vasovasotomy and determine if vasectomy alters prostate growth or function. Project 4 explores the effects of pre-pubertal and adult obstruction on seminiferous epithelium, induction of antisperm antibodies, and characterization of sperm autoantigens. These findings may identify new and important sperm antigens involved in reproductive tract alterations (fertility). Investigators in this P50 share common themes, mechanisms and methods of investigation. These projects represent a refinement and focusing of efforts, building on strengths in reproductive biology and pediatric nephrology at the University of Virginia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK045179-10
Application #
6380723
Study Section
Special Emphasis Panel (SRC (02))
Program Officer
Hoshizaki, Deborah K
Project Start
1992-07-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2003-06-30
Support Year
10
Fiscal Year
2001
Total Cost
$609,462
Indirect Cost
Name
University of Virginia
Department
Urology
Type
Schools of Medicine
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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