Comparative in Vitro and in Vivo Evaluation of the Estrogenic Effect of Hexafluoropropylene Oxide Homologues,Environmental Science & Technology

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Comparative in Vitro and in Vivo Evaluation of the Estrogenic Effect of Hexafluoropropylene Oxide Homologues
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2019-06-28 , DOI: 10.1021/acs.est.9b01579
Yan Xin _{1,

2} , Xiao-Min Ren ₁ , Bin Wan _{1,

2} , Liang-Hong Guo _{1,

2,

3}

Affiliation

As alternatives to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide (HFPO) homologues, including hexafluoropropylene oxide dimer acid (HFPO-DA), hexafluoropropylene oxide trimer acid (HFPO-TA), and hexafluoropropylene oxide tetramer acid (HFPO-TeA), have been used in the fluoropolymer industry for a long period of time. These compounds have attracted widespread attention in recent years due to their environmental ubiquity and high bioaccumulation capability, as well as their toxicity. In our study, we evaluated the potential estrogenic effects of HFPOs in comparison to PFOA by ligand binding, transcriptional activity, and in vivo assays. Fluorescence ligand binding assays showed that both HFPO-TA and HFPO-TeA exhibited higher binding affinity to estrogen receptor ligand binding domains (ER-LBDs) than PFOA, with 2.5- and 57.5-fold higher affinity to ERα-LBD and 2.6- and 41.8-fold higher affinity to ERβ-LBD, respectively, whereas HFPO-DA exhibited weaker binding affinity than PFOA. Unlike PFOA, HFPO-TA and HFPO-TeA exhibited antagonistic activity toward the ERs’ signaling pathway, with HFPO-TeA displaying the strongest potency. In silico study revealed that while PFOA binds with ERs in a similar fashion as 17β-estradiol, the HFPOs display an antagonistic binding mode. Using a zebrafish model, we further found that exposure to HFPO homologues significantly altered the levels of sex steroid hormones and vitellogenin. In general, both in vivo and in vitro results indicate that HFPO homologues might exert higher estrogenic effects than PFOA.

中文翻译：

六氟环氧丙烷同系物的雌激素作用的体外和体内比较比较

作为全氟辛酸（PFOA）的替代品，六氟环氧丙烷（HFPO）的同系物包括六氟环氧丙烷二聚酸（HFPO-DA），六氟环氧丙烷三聚酸（HFPO-TA）和六氟环氧丙烷四聚酸（HFPO-TeA）。在含氟聚合物行业中长期使用。这些化合物由于其环境无处不在和高生物蓄积能力以及它们的毒性而在近年来引起了广泛的关注。在我们的研究中，我们通过配体结合，转录活性和体内试验评估了HFPO与PFOA相比潜在的雌激素作用。荧光配体结合测定表明，HFPO-TA和HFPO-TeA对雌激素受体配体结合域（ER-LBDs）的结合亲和力均高于PFOA，分别为2.5和57。与ERα-LBD的亲和力分别高5倍，与ERβ-LBD的亲和力分别高2.6和41.8倍，而HFPO-DA的结合亲和力比PFOA弱。与PFOA不同，HFPO-TA和HFPO-TeA对ER的信号传导途径表现出拮抗活性，HFPO-TeA显示出最强的效力。电脑研究显示，PFOA与ER结合的方式与17β-雌二醇相似，而HFPO则表现出拮抗结合方式。使用斑马鱼模型，我们进一步发现暴露于HFPO同源物会显着改变性类固醇激素和卵黄蛋白原的水平。通常，体内和体外结果均表明，HFPO同源物可能比PFOA发挥更高的雌激素作用。而HFPO-DA的结合亲和力比PFOA弱。与PFOA不同，HFPO-TA和HFPO-TeA对ER的信号传导途径表现出拮抗活性，HFPO-TeA显示出最强的效力。电脑研究显示，PFOA与ER结合的方式与17β-雌二醇相似，而HFPO则表现出拮抗结合方式。使用斑马鱼模型，我们进一步发现暴露于HFPO同源物会显着改变性类固醇激素和卵黄蛋白原的水平。通常，体内和体外结果均表明，HFPO同源物可能比PFOA发挥更高的雌激素作用。而HFPO-DA的结合亲和力比PFOA弱。与PFOA不同，HFPO-TA和HFPO-TeA对ER的信号传导途径表现出拮抗活性，HFPO-TeA显示出最强的效力。在计算机研究中，PFOA与ER结合的方式与17β-雌二醇相似，而HFPO则显示出拮抗结合方式。使用斑马鱼模型，我们进一步发现暴露于HFPO同源物会显着改变性类固醇激素和卵黄蛋白原的水平。通常，体内和体外结果均表明，HFPO同源物可能比PFOA发挥更高的雌激素作用。电脑研究显示，PFOA与ER结合的方式与17β-雌二醇相似，而HFPO则表现出拮抗结合方式。使用斑马鱼模型，我们进一步发现暴露于HFPO同源物会显着改变性类固醇激素和卵黄蛋白原的水平。通常，体内和体外结果均表明，HFPO同源物可能比PFOA发挥更高的雌激素作用。电脑研究显示，PFOA与ER结合的方式与17β-雌二醇相似，而HFPO则表现出拮抗结合方式。使用斑马鱼模型，我们进一步发现暴露于HFPO同源物会显着改变性类固醇激素和卵黄蛋白原的水平。通常，体内和体外结果均表明，HFPO同源物可能比PFOA发挥更高的雌激素作用。

更新日期：2019-06-29

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