Essential role of neutrophils in germ cell-specific apoptosis following ischemia/reperfusion injury of the mouse testis.
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.
Lysiak
J J
JJ
Department of Urology, The University of Virginia Health Science Center, Charlottesville, VA 22908, USA. jl6n@virginia.edu
Turner
S D
SD
Nguyen
Q A
QA
Singbartl
K
K
Ley
K
K
Turner
T T
TT
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D019040:E-Selectin / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D012670:Seminiferous Epithelium / Q000473:pathology / Q000503:physiopathology; D013733:Testicular Diseases; D013737:Testis / Q000098:blood supply* / Q000473:pathology*; D014102:Torsion Abnormality
D019040:E-Selectin; D017382:Reactive Oxygen Species; D009195:Peroxidase