Santos Rita António, Sousa Ana Paula, Almeida-Santos Teresa, Ramalho-Santos João, Tavares Renata Santos
University of Coimbra, Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Coimbra 3030-789, Portugal.
Center for Neuroscience and Cell Biology, University of Coimbra (CNC-UC), Coimbra 3000-548, Portugal.
Asian J Androl. 2025 Jan 1;27(1):30-36. doi: 10.4103/aja202459. Epub 2024 Aug 13.
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 .
抑郁症目前影响着全球约2.8亿人,其患病率一直在急剧上升,尤其是在年轻人和育龄人群中,这导致抗抑郁药物的消费量增加。抗抑郁药物与男性和女性的性功能障碍都有关;然而,它们在男性生育能力方面的作用几乎没有得到研究。氟西汀和舍曲林这两种5-羟色胺再摄取抑制剂(SSRIs)是全球处方量最大的抗抑郁药物之一。为了确定它们可能产生的影响,将人类精子细胞暴露于舍曲林或氟西汀中,其浓度为先前在接受治疗患者的血液和精液中所发现的浓度。精子在37°C和5%二氧化碳条件下孵育长达24小时,并评估精子活力、存活率、线粒体膜电位、细胞活性氧(ROS)产生、染色质/DNA完整性、顶体状态和酪氨酸磷酸化等重要功能参数。在低水平时,氟西汀在整个时间段内持续降低渐进性运动能力,同时促进ROS水平和精子获能的波动。然而,它并不影响存活率、线粒体膜电位、顶体反应或染色质/DNA完整性。另一方面,舍曲林在低剂量时影响很小或无显著影响,但在超治疗浓度下几乎影响所有测试参数。总之,我们的结果表明,这两种抗抑郁药物都可能损害精子功能,可能通过不同的作用机制,但氟西汀是唯一在体内发现剂量下表现出轻微负面影响的药物。