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.

由于其在消费品和工业应用中的历史用途，全氟辛酸 (PFOA) 在环境中含量丰富。暴露于低剂量 PFOA 与各种疾病风险相关，包括神经系统疾病。然而，潜在的机制仍然知之甚少。在这项研究中，我们检查了 0.4 和 4 μg/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。我们观察到细胞核中 H3K4me3、H3K27me3 和 5 mC 标志物的持续减少，以及从暴露于 0.4 和 4 μg/L PFOA 的 SH-SY5Y 细胞分化而来的 DA 样神经元中核大小和染色质压实百分比的变化。在选定的表观遗传特征中，DNA 甲基化模式可用于区分暴露于 PFOA 的人群和未接触过的人群，这表明参与了表观遗传调控。此外，具有预分化 PFOA 暴露的 DA 样神经元表现出改变的网络连接、线粒体体积和 TH 表达，这意味着 DA 神经元功能受损。总的来说，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，并将表观基因组和线粒体确定为承受长期变化的潜在目标，这些变化有助于增加生命后期神经系统疾病的风险。暗示 DA 神经元功能受损。总的来说，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，并将表观基因组和线粒体确定为承受长期变化的潜在目标，这些变化有助于增加生命后期神经系统疾病的风险。暗示 DA 神经元功能受损。总的来说，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，并将表观基因组和线粒体确定为承受长期变化的潜在目标，这些变化有助于增加生命后期神经系统疾病的风险。