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涕灭威暴露诱导小鼠支持细胞(睾丸支持细胞)的细胞毒性和内质网应激介导的细胞凋亡:对男性不育和环境卫生的影响。

Aminocarb Exposure Induces Cytotoxicity and Endoplasmic Reticulum Stress-Mediated Apoptosis in Mouse Sustentacular Sertoli Cells: Implications for Male Infertility and Environmental Health.

作者信息

Moreira Sílvia, Martins Ana D, Alves Marco G, Pastor Luis Miguel, Seco-Rovira Vicente, Oliveira Pedro F, Pereira Maria de Lourdes

机构信息

Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.

CICECO-Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal.

出版信息

Biology (Basel). 2024 Sep 14;13(9):721. doi: 10.3390/biology13090721.

Abstract

Exposure to pesticides, poses a significant threat to male fertility by compromising crucial cells involved in spermatogenesis. Aminocarb, is a widely used carbamate insecticide, although its detrimental effects on the male reproductive system, especially on sustentacular Sertoli cells, pivotal for spermatogenesis, remains poorly understood. In this study, we investigated the effects of escalating concentrations of aminocarb on a mouse Sertoli cell line, TM4. Assessments included cytotoxic analysis, mitochondrial biogenesis and membrane potential, expression of apoptotic proteins, caspase-3 activity, and oxidative stress evaluation. Our findings revealed a dose-dependent reduction in the proliferation and viability of TM4 cells following exposure to increasing concentrations of aminocarb. Notably, exposure to 5 μM of aminocarb induced depolarization of mitochondria membrane potential, and a significant decrease in the ratio of phosphorylated eIF2α to total eIF2α, suggesting heightened endoplasmic reticulum stress via the activation of the eIF2α pathway. Moreover, the same aminocarb concentration was demonstrated to increase both caspase-3 protein levels and activity, indicating an apoptotic induction. Collectively, our results demonstrate that aminocarb serves as an apoptotic inducer for mouse sustentacular Sertoli cells in vitro, suggesting its potential to modulate independent pathways of the apoptotic cascade. These findings underscore the deleterious impact of aminocarb on spermatogenic performance and male fertility, highlighting the urgent need for further investigation into its mechanisms of action and mitigation strategies to safeguard male fertility.

摘要

接触杀虫剂会通过损害参与精子发生的关键细胞,对男性生育能力构成重大威胁。灭害威是一种广泛使用的氨基甲酸酯类杀虫剂,尽管其对男性生殖系统,尤其是对精子发生至关重要的支持性睾丸支持细胞的有害影响仍知之甚少。在本研究中,我们研究了递增浓度的灭害威对小鼠睾丸支持细胞系TM4的影响。评估内容包括细胞毒性分析、线粒体生物发生和膜电位、凋亡蛋白表达、半胱天冬酶-3活性以及氧化应激评估。我们的研究结果显示,随着灭害威浓度的增加,TM4细胞的增殖和活力呈剂量依赖性降低。值得注意的是,暴露于5μM灭害威会导致线粒体膜电位去极化,并且磷酸化eIF2α与总eIF2α的比率显著降低,这表明通过eIF2α途径的激活导致内质网应激加剧。此外,相同浓度的灭害威被证明会增加半胱天冬酶-3蛋白水平和活性,表明诱导了细胞凋亡。总的来说,我们的结果表明灭害威在体外可作为小鼠睾丸支持细胞的凋亡诱导剂,表明其有可能调节凋亡级联反应的独立途径。这些发现强调了灭害威对精子发生性能和男性生育能力的有害影响,突出了迫切需要进一步研究其作用机制和减轻策略以保护男性生育能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb26/11429014/05a710c0fff8/biology-13-00721-g001.jpg

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