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Abstract

Volume 27, Issue 1 (January 2025) 27, 30–36; 10.4103/aja202459

In vitro effects of antidepressants on human sperm function

António Santos, Rita1,2,3; Sousa, Ana Paula2,3,4; Almeida-Santos, Teresa2,3,4,5; Ramalho-Santos, João2,3,6; Santos Tavares, Renata2,3,6

1University of Coimbra, Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Coimbra 3030-789, Portugal

2Center for Neuroscience and Cell Biology, University of Coimbra (CNC-UC), Coimbra 3000-548, Portugal

3Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3000-548, Portugal

4Reproductive Medicine Unit, Coimbra Hospital and University Centre (CHUC), Coimbra 3004-561, Portugal

5Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal

6Department of Life Sciences, University of Coimbra, Coimbra 3000-456, Portugal

Correspondence: Dr. R Santos Tavares (renata.tavares@cnc.uc.pt)

Originally published: August 13, 2024 Received: December 17, 2023 Accepted: May 20, 2024

Abstract

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% CO2, 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.

Keywords: fluoxetine; human sperm; male fertility; sertraline; sperm function; SSRIs

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.