The effect of silymarin on diabetes mellitus-induced male rats reproductive impairment: Evidences for role of heat shock proteins 70 and 90

Male fertility is adversely influenced by diabetes. The beneficial effects of antioxidant bioflavonoids in improving fertility have been reported. This study was conducted to evaluate the effects of silymarin on diabetes mellitus-induced male reproductive impairment in rats by investigating its role in Hsp70 and Hsp90 expression. To conduct this study, 18 mature male Wistar rats were divided into three groups: control (Con), experimental diabetes type 1 (T1D-sole)-induced, and silymarin (SMN, 120 mg/kg, orally)-treated T1D-induced groups. The testicular total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were evaluated. Tubular differentiation index (TDI), repopulation index (RI), spermiogenesis index (SPI), and the Johnson score were also investigated. The DNA Ladder test was used to evaluate testicular DNA fragmentation, and RNA damage was assessed through fluorescent staining. Immunohistochemical and RT-PCR analyses were performed for Hsp70 and Hsp90. Oral administration of SMN significantly (p<0.05) increased the TAC ratio and decreased the MDA content in testicles compared to the T1D-sole group. The results showed that T1D increased the percentage of seminiferous tubules with negative TDI, RI, and SPI and reduced the Johnson score compared to the Con group (p<0.05). However, treatment with SMN ameliorated the T1D-induced damages to TDI, RI, SPI, and the Johnson score (p<0.05) compared to the T1D group (p<0.05). The staining intensities and the number of Hsp70+ and Hsp90+ cells were significantly higher in the Con group compared to the T1D-sole animals (p<0.05). However, rats treated with SMN showed an increased number of Hsp70+ and Hsp90+ cells per mm² of tissue compared to the T1D-sole group (p<0.05). Diabetes caused DNA fragmentation and RNA damage, but silymarin reduced its negative effects. In conclusion, SMN ameliorates T1D-suppressed spermatogenesis by upregulating testicular antioxidant status and Hsp70 and Hsp90 expression in testicular tissue. Consequently, it can be considered a potential complementary medication for male patients with T1D.