Long-term exposure to environmentally relevant concentrations of hexafluoropropylene oxide dimer acid (GenX) induces trans-generational motor deficits through H3K27 demethylase jmjd-1.2 /PHF8 in Caenorhabditis elegans

IF 7.3 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Pollution Pub Date : 2025-08-11 DOI:10.1016/j.envpol.2025.126981

Chia-Cheng Wei , Chun Ming How , Chi-Wei Huang , Wei-Yun Huang

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Abstract

Hexafluoropropylene oxide dimer acid (GenX) is one of many per-/polyfluoroalkyl substances (PFAS). GenX was developed as a shorter-chain alternative to traditional PFAS due to concerns about their documented toxicity. However, GenX contamination persists, and there has been limited research on its generational adverse effects. This study used Caenorhabditis elegans to evaluate adverse effects of long-term GenX exposure, and its trans-generational locomotive defect. The results showed that C. elegans development was significantly delayed when exposed to 10000 and 30000 μM of GenX; this was accompanied by substantial inhibition of reproduction and locomotion at concentrations ranging from 0.0003 to 10000 μM. Additionally, parental (P0 generation) exposure to environmentally relevant concentrations of GenX (0.0003 and 0.1 μM, or 0.1 and 33.0 μg/L, respectively), with no further exposure in the offspring (F1-F4), resulted in significant trans-generational declines in locomotion in the F1-F3 generations. The mRNA expression analysis found significant alterations in the genes associated with locomotive and epigenetic regulation, unc-17, spr-5, jmjd-1.2, damt-1, and nmad-1, in the P0 generation when exposed to 0.1 μM GenX. The changes in damt-1, nmad-1, spr-5 varied across generations, while a significant decrease in jmjd-1.2 persisted in the F1-F3 generations. No trans-generational effects on locomotion were observed in the jmjd-1.2 mutant strain; this indicates that jmjd-1.2 regulates the trans-generational locomotive defect. In conclusion, long-term exposure to environmentally relevant GenX concentrations induces trans-generational locomotor dysfunction in C. elegans. This is likely mediated by the gene jmjd-1.2, which is linked to both locomotion and epigenetic regulation. These findings provide valuable insights for future GenX generational toxicity evaluations and for assessing the mechanisms involved.

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在秀丽隐杆线虫中，长期暴露于环境相关浓度的六氟环氧丙烷二聚酸（GenX）通过H3K27去甲基化酶jmjd1.2 /PHF8诱导跨代运动缺陷

六氟环氧丙烷二聚酸（GenX）是许多单/多氟烷基物质（PFAS）之一。GenX是作为传统PFAS的短链替代品而开发的，因为人们担心它们的毒性。然而，GenX污染持续存在，对其代际不利影响的研究有限。本研究使用秀丽隐杆线虫来评估长期暴露于GenX的不良影响及其跨代机车缺陷。结果表明，10000 μM和30000 μM的GenX对秀丽隐杆线虫的发育有显著的延缓作用；在0.0003 ~ 10000 μM浓度范围内，小鼠的繁殖和运动均受到明显抑制。此外，亲代（P0代）暴露于环境相关浓度的GenX（分别为0.0003和0.1 μM，或0.1和34.7 μg/L），而后代（F1-F4代）没有进一步暴露，导致F1-F3代的运动能力显着跨代下降。mRNA表达分析发现，当暴露于0.1 μM GenX时，P0代中与运动和表观遗传调控相关的基因unc-17、spr-5、jmjd-1.2、damt-1和nmad-1发生了显著变化。damt-1、nmad-1、spr-5的变化在不同代之间存在差异，而jmjd-1.2的显著下降在F1-F3代中持续存在。在jmjd-1.2突变株中没有观察到运动的跨代影响；这说明jmjd-1.2调节了跨代机车缺陷。总之，长期暴露于与环境相关的GenX浓度会导致秀丽隐杆线虫的跨代运动功能障碍。这可能是由基因jmjd-1.2介导的，该基因与运动和表观遗传调控有关。这些发现为未来GenX世代毒性评估和评估相关机制提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.