State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
Chemosphere. 2013 May;91(8):1099-106. doi: 10.1016/j.chemosphere.2013.01.012. Epub 2013 Feb 8.
Perfluorooctanoic acid (PFOA), a persistent perfluorinated compound, is distributed widely in wildlife and humans. Recent studies showed that PFOA is a suspected endocrine disruptor. But the results are somewhat contradictory and the mechanisms are unclear. In this study, we investigated the endocrine-related effects of PFOA using a series of assays. The lower dose effect of PFOA on development and endocrine-related gene expression were assessed in a short-term zebrafish assay in vivo. To clarify the mechanism of PFOA, in vitro assays were performed. We tested the hormone receptor activities of ER, AR, and TR against PFOA using reporter gene assays. The hormone levels of estradiol (E2) and testosterone (T), the expression of major steroidogenic genes and the key steroidogenic gene regulator steroidogenic factors 1 (SF-1) were measured after PFOA exposure in H295R steroidogenesis assay. Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR. In H295R cells, PFOA could increase the E2 production and decrease the T production, altered the expression of major steroidogenic genes and regulator SF-1. The current findings indicated the potential endocrine-related effects of PFOA and provided novel information for human risk assessment.
全氟辛酸（PFOA）是一种持久性全氟化合物，广泛分布于野生动物和人类中。最近的研究表明，PFOA 是一种疑似内分泌干扰物。但结果有些矛盾，其机制尚不清楚。在这项研究中，我们使用一系列检测方法研究了 PFOA 的与内分泌相关的影响。我们在体内短期的斑马鱼试验中评估了 PFOA 对发育和与内分泌相关的基因表达的低剂量效应。为了阐明 PFOA 的作用机制，我们进行了体外试验。我们使用报告基因检测方法测试了 PFOA 对 ER、AR 和 TR 激素受体的活性。在 H295R 类固醇生成试验中，我们测量了 PFOA 暴露后雌二醇（E2）和睾酮（T）的激素水平、主要类固醇生成基因的表达以及关键类固醇生成基因调节剂 SF-1 的表达。暴露于 PFOA 的斑马鱼胚胎中，esr1、hhex 和 pax 的表达升高。PFOA 能够干扰激素受体 ER 和 TR。在 H295R 细胞中，PFOA 可以增加 E2 的产生，减少 T 的产生，改变主要类固醇生成基因和调节剂 SF-1 的表达。目前的研究结果表明 PFOA 具有潜在的与内分泌相关的影响，并为人类风险评估提供了新的信息。
