GenX暴露诱导hESC来源大脑类器官的神经发育损伤和突触毒性
GenX exposure induces neurodevelopmental impairment and synaptic toxicity in hESC-derived cerebral organoids.
摘要(中文译文)
GenX，也称为六氟环氧丙烷二聚酸（HFPO-DA），于2009年作为一种据称更安全的全氟辛酸（PFOA）替代品被引入。然而，近二十年的使用已引发日益增加的安全性担忧，因为已有报道将其与多种形式的器官损伤相关联。但目前仅有少数研究系统评估了GenX暴露神经毒性的分子机制。本研究旨在利用人胚胎干细胞来源的脑类器官，探究GenX在皮层发育过程中诱导的神经发育损伤和突触毒性。我们发现，早期暴露于GenX导致类器官尺寸减小以及基础神经祖细胞增殖的浓度依赖性缺陷。此外，分化前GenX暴露损害了突触形成并减少了兴奋性突触的数量。我们还发现，早期GenX暴露扰乱了神经活动并改变了神经网络组织。RNA测序和基因本体分析显示，这些效应与神经肽信号通路、突触组装和突触后组织的失调有关。总体而言，神经发生和神经活动方面的这些损伤表明，GenX具有神经毒性效应，并可能构成神经发育障碍的潜在风险因素。
Abstract
GenX, also known as hexafluoropropylene oxide dimer acid (HFPO-DA), was introduced in 2009 as a purportedly safer alternative to perfluorooctanoic acid (PFOA). However, nearly two decades of use have raised increasing safety concerns owing to its reported association with multiple forms of organ damage. However, only a few studies have systematically evaluated the molecular mechanisms underlying the neurotoxicity of GenX exposure. In this study, we aimed to investigate the neurodevelopmental impairments and synaptic toxicity induced by GenX during cortical development using human embryonic stem cell-derived cerebral organoids. We found that early exposure to GenX resulted in reduced organoid size and concentration-dependent deficits in basal neural progenitor cell proliferation. Moreover, GenX exposure prior to differentiation impaired synapse formation and decreased the number of excitatory synapses. We also found that early GenX exposure disrupted neural activity and altered neural network organization. RNA sequencing and Gene Ontology analyses revealed that these effects were associated with dysregulation of neuropeptide signaling pathways, synapse assembly, and postsynaptic organization. Collectively, these impairments in neurogenesis and neural activity indicate that GenX exerts neurotoxic effects and may pose a potential risk factor for neurodevelopmental disorders.
如何引用
AMA
Sung-Ae Hyun, Young-Ju Lee, Moon Yi Ko, Euijun Min, Heejin Park, Younhee Kim, et al. GenX exposure induces neurodevelopmental impairment and synaptic toxicity in hESC-derived cerebral organoids.. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103458.
APA
Sung-Ae Hyun, Young-Ju Lee, Moon Yi Ko, Euijun Min, Heejin Park, Younhee Kim, et al (2026). GenX exposure induces neurodevelopmental impairment and synaptic toxicity in hESC-derived cerebral organoids.. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103458
GB/T 7714
Sung-Ae Hyun, Young-Ju Lee, Moon Yi Ko, Euijun Min, Heejin Park, Younhee Kim, et al. GenX exposure induces neurodevelopmental impairment and synaptic toxicity in hESC-derived cerebral organoids.[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103458.
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