Protective Effects of Fisetin Against Oxidative Stress in Human Sperm: Implications for Cryopreservation

Background: Cryopreservation induces the production of excessive reactive oxygen species (ROS), which decreases sperm physiological functions. Phytochemicals with antioxidant properties, such as fisetin, have shown promising results in reducing oxidative stress (OS). Aim: We aimed to evaluate whether fisetin can counteract the OS exerted on sperm. Methodology: Fisetin (15 and 30 µM) was tested on normozoospermic semen samples that were either frozen in liquid nitrogen or treated with H₂O₂ to induce OS. Sperm motility, sperm viability, mitochondrial membrane potential, metabolic activity, ROS content, lipid peroxidation, reduced glutathione, ATP contents, and apoptosis were tested and compared to controls. Results: The protective effect of fisetin on human sperm was observed against OS-induced stress. Fisetin significantly improved sperm motility, viability, mitochondrial and metabolic activity, and ATP content by reducing OS and lipid peroxidation. Fisetin reduced necrotic cell death and improved sperm survival under H₂O₂-OS. Conclusions: Fisetin protects human sperm from OS, with 30 µM showing greater effectiveness, supporting its potential use in sperm preservation and OS conditions. Further studies are needed to optimize its concentration, elucidate its mechanism of action, and confirm its putative use as an additive in sperm cryoprotective media.