Grape seed extract improved the fertility-enhancing effect of atorvastatin in high-fat diet-induced testicular injury in rats: involvement of antioxidant and anti-apoptotic effects

Objectives Reduced male fertility is highly prevalent with hypercholesterolaemia. Though statins are drugs of choice for hypercholesterolaemia, their effect on male fertility is still controversial and dose-dependent. Grape seed extract (GSE) possess hypocholesterolemic and testicular protective effects. Thus, this study aimed to investigate the effects of low-dose atorvastatin (ATV) on male infertility in hypercholesterolaemic rats and assess the additional value of combining ATV with GSE. Methods Male rats were randomized into four groups. The normal group was fed a standard diet. The remaining groups were fed a high-fat diet (HFD) for 1 month to induce hypercholesterolaemia. Two HFD groups were administered either ATV (1 mg/kg) alone or combined with GSE (200 mg/kg) orally for 65 days, while the third group served as HFD control. Key findings Treatment with ATV or ATV/GSE attenuated dyslipidemia-induced alteration in serum HDL-cholesterol, LDL-cholesterol, and total cholesterol. ATV enhanced serum testosterone, sperm count and motility and fertility index. The effect on testosterone and sperm count was more pronounced by ATV/GSE. Moreover, ATV reduced testicular malondialdehyde, nitric oxide, caspase-9 and caspase-3 while elevated reduced glutathione and superoxide dismutase along with catalase activity. Noteworthy, GSE/ATV induced more powerful antioxidant and anti-apoptotic effects. Conclusion GSE enhanced ATV's protective effect against hypercholesterolaemia-induced infertility via antioxidant and anti-apoptotic mechanisms.