摘要
No AccessJournal of UrologyOriginal Articles1 Dec 2004THE MOLECULAR PATHOLOGY OF EXPERIMENTAL TESTICULAR TORSION SUGGESTS ADJUNCT THERAPY TO SURGICAL REPAIR TERRY T. TURNER, HYUN J. BANG, and JEFFERY L. LYSIAK TERRY T. TURNERTERRY T. TURNER More articles by this author , HYUN J. BANGHYUN J. BANG More articles by this author , and JEFFERY L. LYSIAKJEFFERY L. LYSIAK More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000144203.30718.19AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and 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-α and interleukin-1β, 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. References 1 : Acute scrotal pain. Emerg Med Clin North Am1998; 16: 781. Google Scholar 2 : The fate of the human testis following unilateral torsion of the spermatic cord. Br J Urol1996; 58: 698. Google Scholar 3 : Old and new aspects of testicular torsion. Semin Urol1998; 4: 146. Google Scholar 4 : The effect of allopurinol pretreatment before testicular torsion. J Urol1994; 161: 1715. Google Scholar 5 : Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod1997; 57: 1267. Google Scholar 6 : Testis after torsion. Br J Surg1978; 50: 43. Google Scholar 7 : Glutathione, oxidative stress, and aging. Age1996; 19: 129. Google Scholar 8 : Comparison of hexachlorocyclohexane-induced oxidative stress in the testis of immature and adult rats. Com Biochem Physiol1998; 118: 319. Google Scholar 9 : Oxidative stress in testes of rats subjected to chronic ion intoxication and γ-tocopherol supplementation. Toxicology1999; 132: 179. Google Scholar 10 : Fertility after torsion of the spermatic cord. Br J Urol1990; 65: 225. Google Scholar 11 : Acute experimental testicular torsion: no effect on contralateral testis. J Androl1985; 6: 65. Google Scholar 12 : On unilateral testicular and epididymal torsion: no effect on the contralateral testis. J Urol1987; 138: 1285. Link, Google Scholar 13 : Spermatic cord torsion: loss of spermatogenesis despite return blood flow. Biol Reprod1993; 49: 401. Google Scholar 14 : Leydig cell function after experimental testicular torsion despite loss of spermatogenesis. J Androl1995; 16: 12. Google Scholar 15 : Fertility after experimental torsion of the spermatic cord. Urologe Ausg A1980; 19: 303. Google Scholar 16 : Experimental aspects of testicular torsion. Dial Ped Urol1985; 8: 2. Google Scholar 17 : The effect of unilateral testicular torsion on the contralateral testicle in prepubertal Chinese hamsters. J Pediatr Surg1985; 20: 592. Google Scholar 18 : Prepubertal testicular torsion: subsequent fertility. J Pediatr Surg1985; 20: 598. Google Scholar 19 : Testicular histology in children with unrelated testicular torsion. J Urol1986; 136: 208. Google Scholar 20 : Torsion of the testis and allied conditions. Br J Surg1976; 63: 465. Google Scholar 21 : New animal model to evaluate testicular blood flow during testicular torsion. J Pediatr Surg1999; 34: 1004. Google Scholar 22 : Essential role of neutrophils in germ cell-specific apoptosis. Biol Reprod2001; 65: 718. Google Scholar 23 : Fluctuations in rat testicular interstitial oxygen tensions are linked to testicular vasomotion. Biol Reprod2000; 63: 1383. Google Scholar 24 : On the synthesis and secretion of seminiferous tubule proteins in vivo after ischemia and germ cell loss. Biol Reprod1996; 57: 1275. Google Scholar 25 : Apoptosis in the pathogenesis and treatment of disease. Science1995; 267: 1456. Google Scholar 26 : Apoptosis: pathophysiology of programmed cell death. Path Res Pract1996; 192: 676. Google Scholar 27 : Apoptotic pathways: the road to ruin. Cell1998; 94: 695. Google Scholar 28 : The biochemistry of apoptosis. Nature2000; 407: 770. Google Scholar 29 : The Bcl-2 protein family: arbiters of cell survival. Science1998; 281: 1322. Google Scholar 30 : Glucocorticoid-induced thymocyte apoptosis is associated with endogenous nuclease activation. Nature1980; 284: 555. Google Scholar 31 : Apoptosis by death factor. Cell1997; 88: 355. Google Scholar 32 : CD95′s deadly mission in the immune system. Nature1998; 407: 789. Google Scholar 33 : Regulation of germ cell death in mammalian gonads. APMIS1998; 108: 142. Google Scholar 34 : Identification of male germ cells undergoing apoptosis in adult rats. J Reprod Fertil1995; 105: 25. Google Scholar 35 : Experimental cryptorchidism induces germ cell apoptosis by p53-dependent and independent pathways in mice. Biol Reprod1998; 58: 494. Google Scholar 36 : The fas system in a key regulator of germ cell apoptosis in the testis. Endocrinology1997; 138: 2081. Google Scholar 37 : Sensitivity of testicular germ cells to toxicant-induced apoptosis in gld mice that express nonfunctional fas ligand. Endocrinology2000; 141: 787. Google Scholar 38 : Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis. Biol Reprod2000; 63: 1465. Google Scholar 39 : Oxygen Radicals and Tissue Injury. Bethesda: Upjohn1988: 34. Google Scholar 40 : Mechanisms that regulate the function of selectins and their ligands. Physiol Rev1999; 79: 181. Google Scholar 41 : Ischemia-reperfusion of the murine testis stimulates the expression of proinflammatory cytokines and activation of c-jun N-terminal kinase in a pathway to E-selectin expression. Biol Reprod2003; 69: 202. Google Scholar 42 : Oxidative stress upregulates IL-8 and TNFα synthesis by human dendritic cells. Eur J Immunol1998; 28: 3886. Google Scholar 43 : Molecular mechanisms of tumor necrosis factor α gene expression in monocytic cells via hyperglycemia induced oxidant stress. J Biol Chem2000; 275: 17728. Google Scholar 44 : Tumor necrosis factor α induced E-selectin expression is activated by NFκB and c-Jun N terminal kinase/p38 pathways. J Biol Chem1997; 272: 2753. Google Scholar 45 : Rescue of testicular function after acute experimental torsion. J Urol1997; 157: 340. Link, Google Scholar 46 : Peptide and nonpeptide reactive oxygen scavengers provide partial rescue of the testis after torsion. J Androl2002; 23: 400. Google Scholar From the Departments of Urology and Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byWatson M, Bartkowski D and Nelson N (2014) Intracompartmental Pressure as a Predictor of Intratesticular Blood Flow: A Rat ModelJournal of Urology, VOL. 193, NO. 6, (2062-2067), Online publication date: 1-Jun-2015.Jiang D, Wu D, Zhang Y, Xu B, Sun X and Li Z (2012) Protective Effects of Hydrogen Rich Saline Solution on Experimental Testicular Ischemia-Reperfusion Injury in RatsJournal of Urology, VOL. 187, NO. 6, (2249-2253), Online publication date: 1-Jun-2012.Yang S, Shih H, Chow Y, Wang T, Tsai P and Huang C (2010) Simvastatin Attenuates Testicular Injury Induced by Torsion-DetorsionJournal of Urology, VOL. 184, NO. 2, (750-756), Online publication date: 1-Aug-2010.Yang S, Shih H, Chow Y, Tsai P and Huang C (2008) Hemin Induced Heme Oxygenase-1 Over Expression Involves Nuclear Factor-E2 Related Factor-2, Nuclear Factor-κB and Extracellular Regulated Kinase: An Experimental Study in a Testicular Torsion-Detorsion Rodent ModelJournal of Urology, VOL. 179, NO. 6, (2456-2463), Online publication date: 1-Jun-2008. (2007) Reply by AuthorsJournal of Urology, VOL. 178, NO. 3, (1017-1017), Online publication date: 1-Sep-2007.Yang S, Shih H, Chow Y, Tsai P, Wang T, Wang P and Huang C (2018) The Protective Role of Heme Oxygenase-1 Induction on Testicular Tissues After Testicular Torsion and DetorsionJournal of Urology, VOL. 177, NO. 5, (1928-1933), Online publication date: 1-May-2007. Volume 172Issue 6 Part 2December 2004Page: 2574-2578 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsoxidative stresstesticular torsiontestisspermatogenesisapoptosisMetricsAuthor Information TERRY T. TURNER More articles by this author HYUN J. BANG More articles by this author JEFFERY L. LYSIAK More articles by this author Expand All Advertisement PDF downloadLoading ...