Resveratrol improves asthenozoospermia by mitigating oxidative stress-induced mitochondrial dysfunction

To investigate the protective effects and mechanisms of resveratrol against oxidative stress-induced sperm dysfunction in vitro and cyclophosphamide-induced asthenozoospermia in vivo.

An H₂O₂-induced sperm oxidative stress model was established to evaluate the dose-dependent effects of resveratrol on viability, motility, reactive oxygen species (ROS), lipid peroxidation, antioxidant enzymes, mitochondrial function, and apoptosis. A cyclophosphamide-induced asthenozoospermic mouse model was used to assess in vivo efficacy on sperm quality and testicular antioxidant capacity.

Resveratrol significantly improved sperm viability, total motility, and progressive motility in a dose-dependent manner. It reduced ROS generation and malondialdehyde (MDA) levels while enhancing antioxidant enzyme activities. Mitochondrial function was enhanced, as evidenced by maintained membrane potential, increased Adenosine Triphosphate (ATP) production, elevated succinate dehydrogenase activity, and preserved mitochondrial ultrastructure. Furthermore, resveratrol suppressed mitochondrial-mediated apoptosis by modulating B-cell Lymphoma 2 (Bcl-2) family protein ratios. In vivo, resveratrol treatment markedly improved sperm parameters and testicular antioxidant capacity in asthenozoospermic mice.

Resveratrol protects sperm against oxidative damage through multiple mechanisms, including antioxidative, mitochondria-preserving, and anti-apoptotic pathways. These findings support its potential as a therapeutic candidate for male infertility associated with oxidative stress.