The molecular mechanism behind insulin protective effects on testicular tissue of hyperglycemic rats.

Aims: The present study assessed the possible mechanisms by which the insulin regulates the heat shock (HSPs) and transitional proteins expression and consequently ameliorates the oxidative stress-induced damages in germ and sperm cells DNA contents.

Main Methods: Mature male Wistar rats were distributed into control, Hyperglycemia-induced (HG) and insulin-treated HG-induced (HG-I) groups. Following 8 weeks from HG induction, testicular total antioxidant capacity (TAC), immunoreactivity of 8-oxodG, germ cells mRNA damage, Hsp70-2a, Hsp90, transitional proteins 1 and 2 (TP-1 and -2) mRNA and protein expressions were analyzed. Moreover, the sperm chromatin condensation was assessed by aniline-blue staining, and DNA integrity of germ and sperm cells were analyzed by TUNEL and acrdine-orange staining techniques.

Key Findings: The HG animals exhibited significant (p < 0.05) reduction in TAC, HSp70-2a, TP-1 and TP-2 expression levels, and increment in 8-oxodG immunoreactivity, mRNA damage, and Hsp90 expression. However, insulin treatment resulted in (p < 0.05) enhanced TAC level, Hsp70-2a, Hsp90, TP-1 and TP-2 expressions, besides reduced 8-oxodG immunoreactivity and mRNA damage compared to the HG group (p < 0.05). The chromatin condensation and the germ and sperm cells DNA fragmentation were decreased in HG-I group.

Significance: Insulin treatment amplifies the testicular TAC level, improves the Hsp70-2a, TP-1, and TP-2 expressions, and boosts the Hsp90-mediated role in DNA repairment process. Consequently, altogether could maintain the HG-induced DNA integrity in the testicular and sperm cells.