Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the notch 2/jagged 1/hes-1 and caspase-8 pathways

The aim of the study is to examine the role of matrix metalloproteinases (mmps) and their inhibitors (timp) during testicular ischemia/reperfusion (t i/r). the involvement of the notch pathway,and their modulation by the antioxidant genistein is also studied. three groups of male sprague-dawley rats were used: sham rats,t i/r rats,and genisteintreated rats (10 mg/kg). the t i/r rat model underwent testicular artery occlusion of the left testis and was subjected to 60 min ischemia followed by 4 h reperfusion. protein expression of mmp-2,mmp-9,timp-1,and timp-2 were measured in testicular tissue. histological examination was performed to assess spermatogenesis. protein levels of notch 2,jagged 1,and hairy/enhancer of split 1 (hes-1) was quantified. the degree of testicular oxidative stress,dna damage and germ cell apoptosis were also evaluated. t i/r induced severe tubular damage,a significant increase in mmp-2 and mmp-9 expression and decreased expression timp-1 and timp-2. genistein treatment normalized the mmp-timp imbalance. rats subjected to t i/r had low total antioxidant capacity of the testis,decreased superoxide dismutase activity,and increased oxidative dna damage. enhanced activities of caspase 8,caspase 3 and parp were also observed during t i/r. genistein reversed the t i/r-induced suppression of the notch 2/jagged 1/hes-1 pathway. genistein was also able to salvage the testicular structure and function through restoring the mmp-timp anti-proteolytic balance,suppressing spermatogenic damage,alleviating oxidative stress and apoptosis. the notch pathway is partly involved in inhibiting the t i/r-induced testicular impairment. © 2016,polish physiological society. all right reserved.