In vitro effects of antidepressants on human sperm function.

Asian journal of andrology Pub Date : 2025-01-01 Epub Date: 2024-08-13 DOI:10.4103/aja202459
Rita António Santos, Ana Paula Sousa, Teresa Almeida-Santos, João Ramalho-Santos, Renata Santos Tavares
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Abstract

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% 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 .

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抗抑郁药对人类精子功能的体外影响。
目前,全世界约有 2.8 亿人受到抑郁症的影响,其发病率正在急剧上升,尤其是在年轻人和育龄人群中,这也导致了抗抑郁药物用量的增加。抗抑郁药与男性和女性的性功能障碍都有关联,但它们对男性生育力的影响却鲜有研究。氟西汀和舍曲林这两种血清素再摄取抑制剂(SSRIs)是全球处方量最多的抗抑郁药。为了确定这两种药物可能产生的影响,我们将人类精子细胞暴露于舍曲林或氟西汀中,其浓度以前曾在接受治疗的患者的血液和精液中发现过。精子在 37°C 和 5% CO2 条件下培养长达 24 小时,并对精子的活力、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进行评估。在低浓度下,氟西汀会持续降低精子的运动能力,同时促进 ROS 水平的波动和精子获能。然而,氟西汀不会影响精子活力、线粒体膜电位、顶体反应或染色质/DNA完整性。另一方面,舍曲林在低剂量时几乎没有影响,但在超治疗浓度时几乎影响所有测试参数。总之,我们的研究结果表明,这两种抗抑郁药可能会通过不同的作用机制损害精子功能,但在体内发现的剂量下,氟西汀是唯一表现出轻微负面影响的药物。
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