BDE-47通过干扰线粒体功能和与胆固醇转运相关的基因来降低BeWo细胞中的孕酮水平。,Chemical Research in Toxicology

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BDE-47通过干扰线粒体功能和与胆固醇转运相关的基因来降低BeWo细胞中的孕酮水平。
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2019-02-15 , DOI: 10.1021/acs.chemrestox.8b00312
Anqi Shan _{1,

2} , Mengxue Li _{1,

2} , Xuejun Li _{1,

2} , Yaoyan Li _{1,

2} , Mengfan Yan _{1,

2} , Ping Xian _{1,

2} , Ying Chang ₃ , Xi Chen _{1,

2} , Nai-Jun Tang _{1,

2}

Affiliation

据报道，多溴联苯醚（PBDEs）具有生殖内分泌毒性，但该过程的机制尚不清楚。当前可用的研究集中于类固醇生成过程中的酶促反应，但结果不一致。在这项研究中，我们探索了2,2'，4,4'-四溴二苯醚（BDE-47）对孕酮生物合成的影响以及人胎盘绒毛膜癌细胞的潜在机制。结果表明，BDE-47以剂量依赖的方式降低了孕酮的产生，但对关键酶（Cyp11a1和3β-HSD）没有影响。BDE-47暴露可使线粒体膜电位去极化，并下调三磷酸腺苷水平。Mfn2，Tspo，Atad3，Vdac1，Fis1和Drp1的基因表达水平，参与线粒体动力学和胆固醇运输的细胞被扰乱。在1μMBDE-47暴露组中诱导了线粒体生物标志物的某些CpG位点（Drp1，Opa1，Vdac2和Atad3）的去甲基化，但在50μM处理下未观察到甲基化变化。我们的发现表明，BDE-47诱导的孕酮合成减少可能与胆固醇转运，线粒体动力学和线粒体功能有关。这些发现提供了有关多溴二苯醚的生殖内分泌毒性的大量数据。我们的发现表明，BDE-47诱导的孕酮合成减少可能与胆固醇转运，线粒体动力学和线粒体功能有关。这些发现提供了有关多溴二苯醚的生殖内分泌毒性的大量数据。我们的发现表明，BDE-47诱导的孕酮合成减少可能与胆固醇转运，线粒体动力学和线粒体功能有关。这些发现提供了有关多溴二苯醚的生殖内分泌毒性的大量数据。

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BDE-47 Decreases Progesterone Levels in BeWo Cells by Interfering with Mitochondrial Functions and Genes Related to Cholesterol Transport.

Polybrominated diphenyl ethers (PBDEs) have been reported to exert reproductive endocrine toxicity, but the mechanisms for this process remain unclear. Currently available studies have concentrated on the enzymatic reactions during steroidogenesis, but the results are not consistent. In this study, we explored the effects of 2,2',4,4'-tertrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and the potential mechanisms in human placental choriocarcinoma cells. The results showed that BDE-47 decreased progesterone production in a dose-dependent manner but had no effect on key enzymes (Cyp11a1 and 3β-HSD). BDE-47 exposure depolarized the mitochondrial membrane potential and downregulated adenosine triphosphate levels. The gene expression levels of Mfn2, Tspo, Atad3, Vdac1, Fis1, and Drp1, which are involved in mitochondrial dynamics and cholesterol transport, were disturbed. The demethylation of some CpG loci of mitochondrial biomarkers (Drp1, Opa1, Vdac2, and Atad3) was induced in the 1 μM BDE-47 exposure group, but no methylation change was observed with 50 μM treatment. Our findings unveiled that the reduction of progesterone synthesis induced by BDE-47 might be associated with cholesterol transportation, mitochondrial dynamics, and mitochondrial functions. These findings provide substantial data on the reproductive endocrine toxicity of PBDEs.

更新日期：2019-02-04

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