Germ Cell Apoptosis and Oxidative DNA Damage in Testicular Ischemia Reperfusion Injury: Survivin’ the Lipoxygenases

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ObjectiveTesticular ischemia reperfusion injury (tIRI) is widely accepted as the underlying mechanism for the pathophysiology of testicular torsion and detrorsion (TTD) in young children that could increase the risk of male infertility. The aim of this study is to examine the role of the pro‐oxidative lipoxygenases (LOXs)‐induced testicular oxidative stress in the etiology of tIRI‐induced germ cell apoptosis (GCA) and oxidative DNA damage using its potent selective inhibitor nordihydroguaiaretic acid (NDGA).Materials and methodsSprague‐Dawley male rats (n = 36, 8 weeks old, 250–300g) were randomly assigned to three groups: Sham, unilateral tIRI and tIRI + NDGA (25 mg/kg). Rats underwent 1 hour ischemia followed by 4 hours reperfusion. Harvested testes were evaluated for spermatogenic damage by H&E staining, oxidative DNA damage by biochemical assays, GCA, and tissue immunoexpression of the three LOXs (LOX‐5, ‐12 and ‐15). The induction of GCA and the involvement of the apoptosis pathways survivin/ASK‐1/JNK and was investigated by immunofluorescence staining.ResultsOur data showed that tIRI caused disorganization of the seminiferous tubules layers and significant spermatogenic damage. Increased LOX immunoexpression but not mRNA expression was calculated as a result of tIRI. Augmented levels of LOX‐induced protein, lipid, and DNA oxidative damage were significantly elevated during tIRI. In addition, tIRI activated the ASK‐1/JNK signaling pathway, which was associated with the down regulation of survivin, an inhibitor of apoptosis. Selective inhibition of LOXs by NDGA diminished the above tIRI‐induced changes.ConclusionThe study outcomes implicates the role of LOXs in the generation of reactive oxygen species, which partly contributed to the tIRI‐induced oxidative damage that also led to spermatogenic damage, oxidative DNA damage and induction of the apoptosis pathway survivin/ASK‐1/JNK. This new finding provides a good understanding to the tIRI/TTD mechanism in the field of translational medicine worldwide.Support or Funding InformationKuwait Foundation for the Advancement of Science (KFAS), Kuwait – Project Code: P116‐13MB‐01.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.