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氟西汀通过破坏抗氧化防御系统和改变凋亡相关基因的表达来降低人类精子质量:一项体外研究。

Fluoxetine Mitigates Human Sperm Quality by Disrupting the Antioxidant Defense System and Altering the Expression of Apoptosis-Related Genes: An In Vitro Study.

作者信息

Roostaee Zahra, Mehranjani Malek Soleimani, Cheraghi Ebrahim

机构信息

Department of Biology, Faculty of Science, Arak University, PO Box 384-817758, Sardasht, Arak, 384817758, Iran.

Department of Biology, Faculty of Science, University of Qom, Qom, 3716146611, Iran.

出版信息

Reprod Sci. 2025 Feb;32(2):326-342. doi: 10.1007/s43032-024-01760-z. Epub 2025 Jan 9.

DOI:10.1007/s43032-024-01760-z
PMID:39789370
Abstract

Fluoxetine is used in the management of depression, anxiety and other mood disorders by increasing serotonin levels in the brain and can cause sexual side effects by changing the homeostasis of sex hormones and increasing oxidative stress. Since many men who take fluoxetine are of reproductive age and sperm are exposed to fluoxetine for a considerable time, this study aimed to examine the in vitro effects of fluoxetine on human sperm biochemical markers and sperm parameters. Semen samples from 30 fertile men were divided into three groups: a positive control group, a negative control group and a fluoxetine-treated group. We investigated sperm parameters, mitochondrial membrane potential (MMP), acrosome reaction, DNA fragmentation, chromatin integrity, and the expression of CASPASE8, CASPASE9, BAX, and BCL2 genes and proteins. Data were analyzed using repeated measures analysis. The results showed that the average percentage of motility, viability, MMP, acrosome and chromatin integrity, total antioxidant capacity (TAC) level, and BCL2 gene and protein expression in the fluoxetine group were significantly reduced compared to the positive and negative control groups. While the average percentage of non-progressive motility, sperm DNA fragmentation, malondialdehyde (MDA) level, reactive oxygen species (ROS), gene and proteins expression of CASPASE8, CASPASE9 and BAX increased significantly. This study suggests that fluoxetine may impair sperm quality by increasing the expression of apoptotic genes, proteins, and oxidative stress. Therefore, careful management of fluoxetine in treating depression is crucial, especially in men of reproductive age, due to its potential sexual side effects. HIGHLIGHTS: • Fluoxetine reduces the quality of human sperm by inducing oxidative stress. • Fluoxetine lowers the total antioxidant capacity in human sperm by increasing ROS. • Fluoxetine increases the expression of apoptosis genes in human sperm.

摘要

氟西汀通过提高大脑中的血清素水平用于治疗抑郁症、焦虑症和其他情绪障碍,并且可通过改变性激素的稳态和增加氧化应激导致性功能方面的副作用。由于许多服用氟西汀的男性处于生育年龄,精子会在相当长的时间内接触氟西汀,因此本研究旨在检测氟西汀对人类精子生化标志物和精子参数的体外影响。将30名有生育能力男性的精液样本分为三组:阳性对照组、阴性对照组和氟西汀治疗组。我们研究了精子参数、线粒体膜电位(MMP)、顶体反应、DNA片段化、染色质完整性以及CASPASE8、CASPASE9、BAX和BCL2基因及蛋白的表达。采用重复测量分析对数据进行分析。结果显示,与阳性和阴性对照组相比,氟西汀组的活力、存活率、MMP、顶体和染色质完整性的平均百分比、总抗氧化能力(TAC)水平以及BCL2基因和蛋白表达均显著降低。而非进行性运动的平均百分比、精子DNA片段化、丙二醛(MDA)水平、活性氧(ROS)、CASPASE8、CASPASE9和BAX的基因及蛋白表达则显著增加。本研究表明,氟西汀可能通过增加凋亡基因、蛋白的表达以及氧化应激来损害精子质量。因此,鉴于其潜在的性功能副作用,在治疗抑郁症时谨慎使用氟西汀至关重要,尤其是对处于生育年龄的男性。要点:• 氟西汀通过诱导氧化应激降低人类精子质量。• 氟西汀通过增加ROS降低人类精子的总抗氧化能力。• 氟西汀增加人类精子中凋亡基因的表达。

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