Humanin Preserves Sperm Quality and Natural Mating Fertility After Testicular Ischemia-Reperfusion Injury in Mice

Testicular torsion-detorsion induces ischemia-reperfusion (I/R) injury that compromises sperm quality and fertility, yet whether mitochondrial-derived peptides can mitigate this damage has not previously been examined. This study investigated the dose-dependent protective effects of humanin, an endogenous mitochondrial-derived cytoprotective peptide, on epididymal sperm parameters and natural mating fertility following testicular I/R injury in mice. Adult male mice underwent ۷۲۰° testicular torsion for two hours followed by detorsion, with or without a single intraperitoneal dose of humanin (۱۲۶, ۲۵۲, or ۵۰۴ µg/kg) administered thirty minutes before reperfusion. Sperm concentration and motility were assessed by computer-assisted sperm analysis (CASA); viability, DNA integrity, and membrane functional competence were evaluated by eosin-nigrosin staining, acridine orange fluorescence, and the hypo-osmotic swelling test, respectively; and fertility outcomes were determined by natural mating trials with untreated females. Untreated I/R animals exhibited marked reductions in sperm concentration, motility, and DNA integrity, together with a near-complete collapse in pregnancy index (۷%) and male fertility index (۱۴%) relative to sham-operated controls. Humanin treatment produced a clear, dose-dependent restoration of all sperm-functional parameters, with the highest dose (۵۰۴ µg/kg) restoring pregnancy and male fertility indices to values not statistically different from sham controls (pregnancy index ۸۶% vs. ۱۰۰%; male fertility index ۱۰۰% vs. ۱۰۰%). These findings provide the first evidence that humanin preserves not only sperm quality but also whole-animal fertility after testicular ischemia-reperfusion injury, identifying this peptide as a promising candidate adjunct therapy for reproductive protection in testicular torsion.

کلیدواژه ها:

Humanin ، testicular torsion ، Ischemia-reperfusion injury ، sperm quality ، Male Fertility ، Mtochondrial-derived peptide