Background: Depression, a prevalent mental health condition, impacts countless individuals annually. Fluoxetine, a widely used antidepressant, is valued for its safety and effectiveness. As a selective serotonin reuptake inhibitor, fluoxetine enhances serotonin levels in the brain. However, research suggests that fluoxetine may have detrimental effects on certain cell types, including ovarian epithelial and hippocampal cells, by potentially increasing oxidative stress and contributing to reduced cell survival. Objective: Since many men of reproductive age use fluoxetine to treat their depression, it is essential to investigate its effect on sperm quality. The aim of this study was to evaluate the effect of fluoxetine on motility, viability, DNA fragmentation, and expression of genes related to apoptosis of human sperm in vitro. Materials and Methods: The type of this study was experimental. Semen samples were collected from 30 fertile men and divided into 2 groups including: control (no treatment, 1-hr incubation), and fluoxetine-treated (5 μM fluoxetine, 1-hr incubation). The study evaluated sperm motility (total, progressive, and non-progressive), viability, reactive oxygen species (ROS) levels, and the expression of apoptosis-related genes (BAX, BCL2 and CASPASE3). Data were analyzed using repeated measures analysis. Results: In the fluoxetine group, the mean percentage of total motility, progressive motility, viability, and expression level of the antiapoptotic gene BCL2 showed a significant decrease compared to the control group (p ˂ 0.001), while the mean percentage of non-progressive motility, DNA fragmentation, ROS level, and expression levels of the apoptotic genes BAX and CASPASE3 showed a significant increase in the fluoxetine group compared to the control group (p ˂ 0.001). Conclusion: Our results indicate that fluoxetine negatively impacts human sperm quality in vitro by reducing motility, viability, and anti-apoptotic gene expression, while increasing DNA fragmentation, ROS levels, and apoptotic gene expression. These findings suggest oxidative stress and apoptosis as key mechanisms of damage, raising concerns about its potential effects on male reproductive health.
