Cordycepin mitigates spermatogenic and redox related expression in H2O2-exposed Leydig cells and regulates testicular oxidative apoptotic signalling in aged rats.

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CONTEXT: Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits.

OBJECTIVE: The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H 2 O 2 )-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated.

MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR.

RESULTS: COR treatment (1, 5, and 10 μg/mL) significantly ( p < 0.05 ∼ p < 0.001) inhibited the H 2 O 2 -induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione- S -transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H 2 O 2 -exposed TM3 cells were significantly ( p < 0.05 ∼ p < 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly ( p < 0.05).

CONCLUSION: COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.