Low levels of peroxiredoxins are associated with high iron content and lipid peroxidation in seminal plasma from asthenozoospermic infertile men

Asthenospermia is a common cause of male infertility refers to semen samples with spermatozoa that move slowly or immotile. Recent research has implicated oxidative stress-induced ferroptosis in asthenospermia's pathophysiology. Peroxiredoxins are important players in the antioxidant defense to protect cells against oxidative stress. However, some aspects of the antioxidant response necessary for male fertility are not well understood. This case-control study aimed to elucidate the role of peroxiredoxins in regulating oxidative stress in male fertility via their correlation with ferroptosis. It included 90 fertile and 90 asthenospermic subfertile males from Hilla City, Iraq. Total peroxiredoxin activity, peroxiredoxin-6 level, and peroxiredoxin-4 level were measured alongside the ferroptosis biomarkers glutathione peroxidase-4, malondialdehyde, and the reduced/oxidized protein thiol ratio. Infertile males had significantly higher oxidized thiol and malondialdehyde levels than fertile males (p < 0.05). Total peroxiredoxin activities, peroxiredoxin-6 levels, peroxiredoxin-4 levels, glutathione peroxidase-4 levels, and reduced/oxidized protein thiol ratios were significantly lower in infertile males than in fertile males (p < 0.05). Therefore, peroxiredoxin activity and level correlate with reduced/oxidized protein thiol ratio. They are inversely associated with ferroptosis and directly associated with semen quality. These findings suggest that peroxiredoxins are crucial in preventing ferroptosis and have potential implications for treating asthenospermia.