Transcriptomic analysis reveals chronic PFBA exposure at environmental levels induces liver damage in zebrafish

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2025-09-21 DOI:10.1016/j.aquatox.2025.107584

Biyu Zhang , Tianyu Zheng , Mengjie Chen , Qian Fang , Qiangmei Zhang , Shan Chen , Tianwei Hao , Xubo Wang , Mingzhe Yuan

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Abstract

Perfluorobutanoic acid (PFBA), a short-chain PFAS, is a persistent and bioaccumulative pollutant of increasing ecological concern. However, the long-term effects of environmentally relevant PFBA concentrations on fish liver function remain unclear. In this study, male zebrafish were exposed to 1000 ng/L PFBA for 7, 35, and 64 days to assess hepatotoxicity and molecular alterations over time. Histopathological analysis revealed progressive liver damage, including lipid vacuolization and hemorrhage, which intensified with prolonged exposure. Transcriptome profiling identified thousands of differentially expressed genes (DEGs), with distinct temporal patterns—early immune activation and metabolic disruption (Day 7), peak inflammatory response (Day 35), and partial attenuation or adaptation (Day 64). GO and KEGG analyses highlighted key pathways, including Toll-like receptor (TLR), Mammalian Target of Rapamycin (mTOR), Peroxisome Proliferator-Activated Receptor (PPAR) , and Mitogen-Activated Protein Kinase (MAPK) pathways. qPCR validation of TLR pathway genes (tlr1, tlr2, tlr3, tlr5, tlr7, tlr8, pik3cd, pik3r2, akt3b, akt1, mapk1, mapk3, mapk11, mapk14, nfκb1, tab2, il-8, tnfα) confirmed the upregulation of these genes, supporting the findings from transcriptome analysis and highlighting the significance of the TLR pathway in the immune response to PFBA exposure. These findings provide valuable insights into the chronic effects of environmentally relevant PFBA exposure on liver function and immune responses in zebrafish, with important implications for understanding the ecological risks of PFBA in aquatic environments.

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转录组学分析显示，环境水平的慢性PFBA暴露会引起斑马鱼的肝脏损伤

全氟丁酸（PFBA）是一种短链PFAS，是一种持久性和生物蓄积性污染物，日益受到生态关注。然而，与环境相关的PFBA浓度对鱼类肝功能的长期影响尚不清楚。在这项研究中，雄性斑马鱼暴露于1000 ng/L PFBA中7天、35天和64天，以评估肝毒性和分子随时间的变化。组织病理学分析显示进行性肝损伤，包括脂质空泡化和出血，随着暴露时间的延长而加剧。转录组分析鉴定了数千个差异表达基因（DEGs），具有不同的时间模式-早期免疫激活和代谢中断（第7天），炎症反应高峰（第35天）和部分衰减或适应（第64天）。GO和KEGG分析强调了关键途径，包括toll样受体（TLR）、哺乳动物雷帕霉素靶点（mTOR）、过氧化物酶体增殖物激活受体（PPAR）和丝裂原激活蛋白激酶（MAPK）途径。TLR通路基因（tlr1、tlr2、tlr3、tlr5、tlr7、tlr8、pik3cd、pik3r2、akt3b、akt1、mapk1、mapk3、mapk11、mapk14、nfκb1、tab2、il-8、tnfα）的qPCR验证证实了这些基因的上调，支持了转录组分析的结果，强调了TLR通路在PFBA暴露免疫应答中的重要意义。这些发现为了解环境相关的PFBA暴露对斑马鱼肝功能和免疫反应的慢性影响提供了有价值的见解，对了解水生环境中PFBA的生态风险具有重要意义。

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

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.