AIMTo evaluate the immunohistopathological changes in the contralateral testis of rats after an experimental spermatic cord torsion.

METHODSMale Sprague-Dawley rats of 45-50 days old were subjected to a 720 degree unilateral spermatic cord torsion for 10, 30 and 80 days (experimental group, E), respectively or sham operation (control group, C). Histopathology of the contralateral testis as well as germ cell apoptosis were studied using the Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique. The number of testicular lymphocytes, mast cells and macrophages, and the expression of tumor necrosis factor-alpha (TNF-alpha) and its receptor (TNFR1) in testicular cells of the contralateral testis were quantified by histochemistry and immunohistochemistry. TNF-alpha concentration in testicular fluid was determined by ELISA.

RESULTSIn the contralateral testis of rats from the E group, the maximal degree of damage of the germinal epithelium was seen 30 days after torsion. At this time we observed in the E group vs. the C group increases: (i) the number of testicular T-lymphocytes; (ii) the number of testicular mast cells and macrophages; (iii) the percentage of macrophages expressing TNF-alpha; (iv) TNF-a concentration in testicular fluid; (v) the number of apoptotic germ cells; and (vi) the number of TNFR1+ germ cells.

CONCLUSIONExperimental spermatic cord torsion induces, in the contralateral testis, a focal damage of seminiferous tubules characterized by apoptosis and sloughing of germ cells. Results suggest humoral and cellular immune mediated testicular cell damage in which macrophages and mast cells seem to be involved in the induction of germ cell apoptosis through the TNF-alpha/TNFR1 system and in the modulation of the inflammatory process.

Animals ; Apoptosis ; Disease Models, Animal ; Functional Laterality ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; pathology ; Spermatic Cord Torsion ; pathology ; surgery ; Testis ; pathology ; Tumor Necrosis Factor-alpha ; analysis

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination