Background: Fluoxetine is a popular and widely used antidepressant in selective serotonin reuptake inhibitors. Fluoxetine helps treat depression, anxiety, and other mood disorders by increasing serotonin levels in the brain. In vivo studies have shown that an increase in serotonin can cause an increase in prolactin levels, disturbing the male sex hormone system. Therefore, due to the high consumption of fluoxetine, it is necessary to investigate its direct effects on sperm cells in vitro. Objective: Since many users of fluoxetine are at reproductive age, this study aimed to directly investigate the effects of fluoxetine on sperm viability, motility, and acrosome reaction. Materials and Methods: Normal samples of 30 fertile men were collected according to the instructions of the World Health Organization. After liquefaction, each sample was divided into the fresh sperm group, the control group (without treatment and incubated for 1 hr), and the fluoxetine group (treated with 5 µM fluoxetine and incubated for 1 hr). Sperm motility was evaluated according to World Health Organization, viability using eosin-nigrosin staining, and acrosome reaction using fluorescein isothiocyanate-labeled Pisum sativum agglutinin staining. Results: A significant decrease in the mean progressive sperm motility was observed in the fluoxetine group compared to the fresh and control groups (p ≤ 0.001). Also, the percentage of mean sperm viability in the fluoxetine group significantly decreased compared to the fresh and control groups (p ≤ 0.001). A significant increase in the mean percentage of acrosomal reaction was observed in the fluoxetine group compared to the fresh and control groups (p ≤ 0.001). Conclusion: Our study showed that fluoxetine decreases progressive motility and viability and increases acrosome reaction through increasing reactive oxygen species levels, which can disturb male reproductive health.
