Essential Role of Neutrophils in Germ Cell-Specific Apoptosis Following Ischemia/Reperfusion Injury of the Mouse Testis1

Abstract

This study investigates the role of neutrophils in ischemia-induced aspermatogenesis in the mouse. Previous studies in the rat have demonstrated that ischemia-inducing testicular torsion followed by torsion repair and reperfusion resulted in germ cell-specific apoptosis. This was correlated with an increase in neutrophil adhesion to subtunical venules, an increase in reactive oxygen species, and increased expression of several apoptosis-associated molecules. In the present investigation, wild-type C57BL/6 mice were subjected to various degrees and duration of testicular torsion. A torsion of 720 degrees for 2 h caused disruption of the seminiferous epithelium and significantly reduced testis weight and daily sperm production. An immunohistochemical method specific for apoptotic nuclei indicated that these effects were due to germ cell-specific apoptosis. An increase in myeloperoxidase (MPO) activity and an increase in the number of neutrophils adhering to testicular subtunical venules after torsion repair/reperfusion demonstrated an increase in neutrophil recruitment to the testis. In contrast, E-selectin knockout mice and wild-type mice rendered neutropenic showed a significant decrease in neutrophil recruitment as evidenced by MPO activity and microscopic examination of subtunical venules. Importantly, germ cell-specific apoptosis was also reduced. Thus, germ cell-specific apoptosis is observed after ischemia/reperfusion of the murine testis, and this apoptosis is directly linked to the recruitment of neutrophils to subtunical venules. Endothelial cell adhesion molecules, particularly E-selectin, play an important role in mediating this pathology.

Effects of ozone therapy and taurine on ischemia/reperfusion-induced testicular injury in a rat testicular torsion model

“…In the present study, torsion and detorsion-induced I/R injury was found to cause morphological changes and increase the polymorphonuclear cells in the seminiferous tubules, consisting with the literature findings (18). We also observed germinal epithelial cell loss and degenerative changes in spermatogonia and spermatids.…”

Medical perspective in testicular ischemia-reperfusion injury

“…E-selectin acts by tethering neutrophils and facilitating their slow rolling along endothelial cells (53,54). Neutrophil recruitment to affected organs is one of the hallmarks of I/R injury and E-selectin serves a critical role in neutrophil recruitment to the testes following I/R and the resulting germ cell-specific apoptosis (55). Blocking E-selectin with function-blocking monoclonal E-selectin antibody, even after the onset of reperfusion inhibits neutrophil recruitment to the I/R-induced murine testes.…”

Alteration of spermatogenesis following spermatogonial stem cells transplantation in testicular torsion-detorsion mice

“…Unilateral testicular torsion was created by scrotal approach through a midline incision, the left testis twisted 720°in a counter clockwise direction and by fixing the testis to the scrotum with a 6-0 nylon suture passing through the tunica albuginea and dartos [27]. Animals underwent 2 h of unilateral testicular ischemia.…”