PFOS和PFOA对支持细胞的毒性的比较分析。,Environmental Science & Technology

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PFOS和PFOA对支持细胞的毒性的比较分析。
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2020-03-02 , DOI: 10.1021/acs.est.0c00201
Hin Ting Wan ₁ , Keng Po Lai ₂ , Chris Kong Chu Wong ₁

Affiliation

全氟烷基化学物质会引起男性生殖毒性。当前的证据表明化学暴露对睾丸功能恶化和附睾精子数量减少的影响。先前的研究表明，PFOA和PFOS在精浆水平上显示出很高的相关性，但是对精液变量产生了不同的影响。在这项研究中，我们集中于使用大鼠原代支持细胞模型进行的PFOA和PFOS的比较毒性分析。我们的转录组数据显示，PFOA和PFOS处理（40 uM）干扰了整体基因表达。尽管PFOS在影响细胞骨架信号传导，Sertoli细胞-细胞连接和炎症方面诱导了更高的毒性，但Ingenuity途径分析强调了这一点。免疫细胞化学染色显示，PFOS处理（40和80 uM）诱导了肌动蛋白丝的截短和细胞质中束缚的束缚构型。此外，N-钙粘蛋白（N-cad）和β-连环蛋白（β-cat）的无序分布以及Sertoli细胞-细胞界面处ZO-1的碎片均很明显。在80μM的全氟辛烷磺酸下，观察到N-cad，β-cat和ZO-1的细胞质分布。然后，我们检查了多酚抗氧化剂白藜芦醇是否能够保护细胞免受PFOS毒性的影响。用10 uM白藜芦醇对Sertoli细胞进行预处理可防止肌动蛋白丝的截短和β-cat的失调。Western印迹分析表明，Res预处理可增加基础ES蛋白（N-cad和β-cat），紧密连接蛋白（ZO-1和occludin）和缺口连接蛋白的水平，

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Comparative Analysis of PFOS and PFOA Toxicity on Sertoli Cells.

Perfluoroalkyl chemicals induce male reproductive toxicity. Current evidence showed the effects of the chemical exposure on the deterioration of testicular functions, and reduction in epididymal sperm counts. Previous studies showed that PFOA and PFOS displayed a high correlation with each other in seminal plasma levels, but induced different effects on semen variables. In this study, we focused on the comparative toxicity analysis of PFOA and PFOS, using rat primary Sertoli cell model. Our transcriptomic data showed that PFOA and PFOS treatments (40 uM) perturbed global gene expression. While PFOS induced higher toxicity in affecting cytoskeleton signaling, Sertoli cell-cell junction, and inflammation, underlined by Ingenuity pathway analysis. Immunocytochemical staining revealed that PFOS treatment (40 and 80 uM) induced truncated actin filament and disorganized bundled configuration in the cell cytoplasm. Moreover, disorganized distribution of N-cadherin (N-cad) and β-catenin (β-cat), and defragmentation of ZO-1 at the Sertoli cell-cell interface was evident. At 80 M of PFOS, cytoplasmic distribution of N-cad, β-cat, and ZO-1 were observed. We then examined whether resveratrol, a polyphenol anti-oxidant was able to protect the cells from PFOS toxicity. The pretreatment of Sertoli cells with 10 uM resveratrol prevented the formation of truncated actin filament and dis-localization of β-cat. Western blot analysis showed that Res pretreatment increased the levels of basal ES proteins (N-cad and β-cat), tight junction proteins (ZO-1 and occludin), and gap junction protein, versus control.

更新日期：2020-03-06

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