title: The molecular pathology of experimental testicular torsion suggests adjunct therapy to surgical repair.
abstract: OBJECTIVE
  We review the work of our laboratory in discovering the pathophysiological mechanisms that underpin testicular response to testicular torsion. Evidence from animal models is used to discover pathways that might be amenable to manipulation by therapeutic regimens.
  
  
  METHODS
  Rats and mice were subjected to 1 and 2 hours of testicular torsion, respectively. Preliminary experiments determined that those are the times of torsion in those species that produce severe testicular atrophy and germ cell apoptosis. A variety of biochemical and molecular biological techniques were used to determine the mechanism(s) leading to spermatogenic disruption and germ cell apoptosis.
  
  
  RESULTS
  Testicular torsion can eliminate spermatogenesis despite return blood flow, continued Sertoli cell function and perhaps the continued production of testosterone by Leydig cells, although the latter point is not completely resolved. Torsion repair is followed by a period of germ cell apoptosis, accumulation of testicular neutrophils and increased testicular oxidative stress. Testicular vascular E-selectin expression is increased after torsion repair as are a number of cytokines important to the recruitment of neutrophils. Elements of the c-Jun-N-terminal kinase pathway are important in this process. The presence of neutrophils leads to intratesticular oxidative stress, and oxidative stress has been significantly reduced by intravenous infusion of oxygen radical scavengers at the time of torsion repair.
  
  
  CONCLUSIONS
  Testicular torsion causes loss of spermatogenesis and a significant increase in germ cell apoptosis due to an increase in testicular oxidative stress concomitant with reperfusion. Oxidative stress arises with recruitment of neutrophils, and the recruitment of neutrophils occurs due to E-selectin expression on the surface of the testicular venules after torsion repair. The cytokines, tumor necrosis factor-alpha and interleukin-1beta, activate the stress related kinase pathway to E-selectin expression after torsion repair. Oxidative stress is relieved by infusion of oxygen radical scavengers, which results in a significant salvage of testicular function.
authors.affiliation: Departments of Urology and Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA. ttt@virginia.edu
authors.forename: Terry T
authors.initials: TT
authors.lastname: Turner
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Bang
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Lysiak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy; D005854:Germ Cells / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D012039:Regional Blood Flow; D013086:Spermatic Cord Torsion / Q000503:physiopathology* / Q000601:surgery; D013091:Spermatogenesis; D013737:Testis / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D013739:Testosterone / Q000032:analysis
chemical_list: D013739:Testosterone