Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Center for Cancer Research, West Lafayette, IN, 47907, USA.
Environ Pollut. 2022 Sep 1;308:119684. doi: 10.1016/j.envpol.2022.119684. Epub 2022 Jun 25.
Perfluorooctanoic acid (PFOA) is abundant in environment due to its historical uses in consumer products and industrial applications. Exposure to low doses of PFOA has been associated with various disease risks, including neurological disorders. The underlying mechanism, however, remains poorly understood. In this study, we examined the effects of low dose PFOA exposure at 0.4 and 4 μg/L on the morphology, epigenome, mitochondrion, and neuronal markers of dopaminergic (DA)-like SH-SY5Y cells. We observed persistent decreases in H3K4me3, H3K27me3 and 5 mC markers in nucleus along with alterations in nuclear size and chromatin compaction percentage in DA-like neurons differentiated from SH-SY5Y cells exposed to 0.4 and 4 μg/L PFOA. Among the selected epigenetic features, DNA methylation pattern can be used to distinguish between PFOA-exposed and naïve populations, suggesting the involvement of epigenetic regulation. Moreover, DA-like neurons with pre-differentiation PFOA exposure exhibit altered network connectivity, mitochondrial volume, and TH expression, implying impairment in DA neuron functionality. Collectively, our results revealed the prolonged effects of developmental PFOA exposure on the fitness of DA-like neurons and identified epigenome and mitochondrion as potential targets for bearing long-lasting changes contributing to increased risks of neurological diseases later in life.
全氟辛酸（PFOA）由于其在消费产品和工业应用中的历史用途而在环境中大量存在。接触低剂量的 PFOA 与各种疾病风险有关，包括神经紊乱。然而，其潜在机制仍知之甚少。在这项研究中，我们研究了 0.4μg/L 和 4μg/L 低剂量 PFOA 暴露对多巴胺能（DA）样 SH-SY5Y 细胞的形态、表观基因组、线粒体和神经元标志物的影响。我们观察到，暴露于 0.4μg/L 和 4μg/L PFOA 的 DA 样神经元的核内 H3K4me3、H3K27me3 和 5mC 标志物持续减少，核大小和染色质紧缩百分比发生改变。在所选择的表观遗传特征中，DNA 甲基化模式可用于区分暴露于 PFOA 的和未暴露的细胞群体，表明存在表观遗传调控。此外，具有预分化 PFOA 暴露的 DA 样神经元表现出网络连接、线粒体体积和 TH 表达的改变，暗示 DA 神经元功能受损。总之，我们的研究结果揭示了发育性 PFOA 暴露对 DA 样神经元适应性的长期影响，并确定了表观基因组和线粒体作为潜在的靶点，这些靶点可能会发生持久变化，从而增加晚年患神经疾病的风险。
