ABSTRACT
BACKGROUND: There has been a marked increase in the prevalence of childhood and/or adolescent diabetes worldwide. Testicular dysfunction in adult-onset diabetes is well established, whereas the impact of early onset diabetes on the functional development of the testis remains elusive. In the present study we investigated early oxidative impairments and progressive histological changes in streptozotocin (STZ)-induced diabetic prepubertal rat testis. METHODS: Testes were sampled from prepubertal rats injected with a single bolus of STZ (90 mg/kg, i.p.) on Days 1, 3, 5, 7 and 14 after STZ injection for quantitation of testicular oxidative stress parameters in isolated subcellular fractions and mitochondrial and microsomal functional efficiency, as well as at weekly intervals over a period of 8 weeks for histological and flow cytometry analyses. RESULTS: Prepubertal diabetic rats were severely hyperglycemic with reduced testes size. At the subcellular level, a progressive increase in oxidative stress parameters was discernible in the cytosolic and microsomal compartments from Day 1 after STZ, together with decreased antioxidant defenses. Surprisingly, tissue ascorbate and free catalytic iron levels were notably increased in diabetic rat testis. Mitochondrial dysfunction was manifested from Day 5, as evidenced by a reduction in electron transport activity. Histologically, tissue sections showed distorted seminiferous tubules and extensive cell vacuolization with progressive disappearance of spermatids in the lumen by Week 7 after STZ injection, observations that were consistent with flow cytometry data. CONCLUSIONS: Herein we provide evidence that the onset of diabetes brings about oxidative changes at the subcellular level that cumulatively affect the functional growth of testes.
