Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons

Zhao Han; Xie Junkai; Wu ShichenSanchez Oscar F.Zhang XinleFreeman Jennifer L.Yuan Chongli

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Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons

机译：Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons

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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 mu g/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 mu g/L PFOA. Among the selected epigenetic features, DNA methylation pattern can be used to distinguish between PFOAexposed and naive 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.

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《Environmental Pollution》 |2022年第9期|119684.1-119684.12|共12页
作者
Zhao Han; Xie Junkai; Wu ShichenSanchez Oscar F.Zhang XinleFreeman Jennifer L.Yuan Chongli;
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作者单位

Purdue Univ;

Purdue Univ||Purdue Univ Ctr Canc Res;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
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PFOA exposure; PFAS exposure; DNA methylation; Mitochondrion; Epigenome; Dopaminergic neuron;

Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons

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