In vitro effects of antidepressants on human sperm function

• Published in: Asian journal of andrology 2025-01, Vol.27 (1), p.30-36
• Main Authors: Santos, Rita António, Sousa, Ana Paula, Almeida-Santos, Teresa, Ramalho-Santos, João, Tavares, Renata Santos
• Format: Article
• Language: English
• Subjects: Acrosome Reaction - drug effects; Analysis; Antidepressants, Tricyclic; Antidepressive Agents - pharmacology; Cell Survival - drug effects; Fluoxetine; Fluoxetine - pharmacology; human sperm; Humans; Male; male fertility; Membrane Potential, Mitochondrial - drug effects; Motility; Reactive Oxygen Species - metabolism; Selective Serotonin Reuptake Inhibitors - pharmacology; sertraline; Sertraline - pharmacology; Sexual disorders; Sperm; Sperm Capacitation - drug effects; sperm function; Sperm Motility - drug effects; Spermatozoa; Spermatozoa - drug effects; ssris
• ISSN: 1745-7262; 1008-682X; 1745-7262; 1008-682X
• DOI: 10.4103/aja202459

Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO 2 , and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo .