Idebenone improves sperm redox balance and embryo fertilization in a mouse model of diet-induced obesity: In vitro fertilization.

Obesity is a significant factor contributing to male subfertility, primarily through mechanisms such as oxidative stress and compromised sperm function. Nevertheless, the efficacy of targeted antioxidant interventions in restoring sperm competence in non-diabetic obesity remains uncertain. This study aimed to examine the effects of diet-induced obesity on male fertility and to assess whether the supplementation of Idebenone in vitro can enhance sperm function and fertilization outcomes by modulating oxidative stress in a mouse in vitro fertilization (IVF) model. Male C57BL/6J mice were allocated to either ND group (n = 12) or HFD group (n = 13) for a for 12 weeks to develop obesity model. Sperm samples were collected and assessed for concentration, motility, and fertilization capacity using IVF assay. Intracellular ROS levels were measured after in vitro exposure to Idebenone at concentrations of 5 µM and 50 µM. Diet-induced obesity markedly decreased sperm concentration, progressive and total sperm motility, and fertilization rates, all with statistical significance (P < 0.001), and was associated with increased intracellular ROS levels (P < 0.001). In vitro treatment with Idebenone significantly reduced reactive oxygen species (ROS) levels at both 5 µM and 50 µM concentrations (P < 0.001), with a more pronounced reduction at the higher concentration (P < 0.05). Both doses resulted in a significant improvement in sperm motility (P < 0.001). However, only the 5 µM dose significantly enhanced fertilization outcomes (P < 0.05), while the 50 µM dose did not confer additional benefits (P = 0.057). Correlation analyses indicated significant negative associations between body weight and sperm function (P < 0.0001), as well as positive associations between body weight and ROS levels (P < 0.0001). No differences were detected in embryo development. The findings indicate that obesity adversely affects male fertility mainly by disrupting sperm function through oxidative stress. In vitro Idebenone supplementation partially restored sperm function and fertilization capacity by modulating intracellular ROS levels, with optimal effects observed at 5 µM. In contrast, higher concentrations did not confer additional functional benefit, suggesting that excessive ROS suppression may disrupt the finely regulated redox balance required for optimal sperm function.