Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats

OBJECTIVE: To examine the effects of DNase1 treatment on testicular damage after TT aim of this study. It has been demonstrated that testicular torsion (TT) induces thrombus formation and that anticoagulation significantly reduces testicular damage after TT. It was hypothesized that these thrombi are dependent on neutrophil extracellular traps (NETs) and thus NETs disintegration would reduce testicular cell damage.

METHODS: In 10 rats a sham operation was performed. 34 rats underwent induction of iatrogenic TT for 3 hours. After de-torsion and randomization, 24 rats received DNase1 or inactivated DNase1. The following parameters were assessed: testicular damage via Cosetino grading; spermatogenesis via Johnsen score; SCF and cKit, apoptosis via Bax, Bcl2, TUNEL assay and cleaved Caspase3 staining; oxidative stress via SOD, CAT, GPx and MDA; neutrophil recruitment via MPO and NE staining; and NET formation via cfDNA.

RESULTS: 43 rats were included in the study. Subjects treated with DNase1 showed significantly less cellular damage, oxidative stress and apoptosis. Further, DNase1 treated rats demonstrated a significant improvement of spermatogenesis, compared to the controls.

CONCLUSION: The results of the study indicate that thrombus formation during TT is quite likely NET-associated and that dissolution of cell-free DNA (including NETs) significantly improves testicular damage in rats. As treatment with DNase1 reduced apoptosis, oxidative stress, and inflammation, without adversely affecting coagulation, it might be a suitable treatment for (neonatal) TT and ought to be evaluated in humans.