טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSharfman Zavalkovsky Katya
SubjectMechanism of Germ Cell Apoptosis in Ischemic and
Contralateral Testis following Testicular
Ischemia-Reperfusion in a Rat
DepartmentDepartment of Medicine
Supervisors Clinical Professor Jorge Mogilner
Professor Igor Sukhotnik
Full Thesis textFull thesis text - English Version


Abstract

Unilateral spermatic chord torsion leads to ischemia of testicular tissue, detorsion enhances the damage by causing reperfusion. Although the necrosis has long been known as the mechanism of the germ cells death following testicular IR, recent studies showed that apoptosis have an important contribution to the IR induced testicular germ cells loss. Germ cell specific apoptosis after IR of the testis has been shown to be correlated with and dependent on neutrophil recruitment to the testis and that E-selectin expression is critical for neutrophil recruitment to subtunical venules in the testis after IR and for the resultant germ cell-specific apoptosis. Our group showed previously that in addition to ischemic testis, there is a significant increase in germ cells apoptosis in the contralateral testis. The aim of this study was to confirm the damage to the contralateral testis following unilateral testicular torsion and to appreciate its dimensions by appreciating the spermatogenesis parameters, the apoptosis index and by testing for evidence of activation of early steps in intrinsic apoptotic pathway by measuring relative levels of Bax and Bcl-2 mRNA. We also examined the E-selectin expression and PMNs recruitment in the contralateral testis in order to determine the role of these events in germ cell apoptosis in the contralateral testis following unilateral IR. Results: In ischemic testis, bax/bcl-2 ratio did not change significantly, and the elevation of germ cell apoptosis was not marked; in the contralateral testis, germ cell apoptosis increased after 6 hours of reperfusion, achieved statistical significance after 24 hours, and decreased after 72 hours of reperfusion and was initiated by decreased bcl-2 messenger RNA levels and elevated bax/bcl-2 ratio within the first 6 hours of reperfusion. E-selectin expression and neutrophil recruitment increased after one hour and stayed almost unchanged after 6 and 24 hours and apparently may initiate the increase in germ cell apoptosis.

For conclusion: the damage to a contralateral testis in the first 72 hours following unilateral torsion is minimal, comparing to ischemic testis, but it have a potential to  exacerbate, as seen in many patients with folly lost of reproduction ability after such an event. It is important to start an anti inflammation treatment for both testis, as soon as possible because the increase in E-selectin expression and neutrophils recruitment, events which precede the increase in germ cells apoptosis,  were already observed after one hour of reperfusion.