Ivantsova Emma, Sultan Amany, Martyniuk Christopher J
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Animal Health Research Institute, Agriculture Research Center (ARC), Giza 3751254, Egypt.
Toxics. 2025 May 26;13(6):436. doi: 10.3390/toxics13060436.
Per- and polyfluoroalkyl substances (PFAS) are used in consumer products and manufacturing. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) are long-chain PFAS composed of 9, 10, and 11 carbons, respectively, which exert sublethal toxicity to aquatic species. Here, we review the data regarding the environmental fate and ecotoxicology of these understudied long-chain PFAS in fish. The objectives of this study were to (1) compile the literature to compare physiological or molecular signaling pathways disrupted by PFNA, PFDA, or PFUnDA; and (2) uncover potential biomarkers and pathways of toxicity of longer-chain PFAS using gene ontology computational approaches to shed light on their mechanism of action. Studies show that PFAS have a range of effects on fish, including developmental issues, changes in gene expression, and behavioral modifications. Based on our review, PFNA has been studied more frequently in fish compared to PFDA and PFUnDA; however, longer-chained PFAS are proposed to pose greater toxicity. Based on the computational approach, prominent pathways affected by PFNA include insulin signaling ["Insulin -> CEBPA/CTNNB/FOXA/FOXO", "Insulin -> STAT Expression Targets"], immune system signaling ["TNF -> STAT Expression Targets", "IL6 Expression Targets", and "IL2 Expression Targets"], and growth hormone/prolactin signaling ["GH1/PRLR Expression Targets", "PRL/GHR -> STAT Expression Targets", "PRL/PRLR Expression Targets"]. Several transcripts related to cholesterol metabolism were also affected by PFNA. This review summarizes the current knowledge on the distribution, fate, and ecotoxicology of PFNA, PFDA, and PFUnDA in teleost fish, highlighting potential physiological and molecular responses that could aid in assessing long-chain PFAS toxicity in future studies.
全氟和多氟烷基物质（PFAS）用于消费品和制造业。全氟壬酸（PFNA）、全氟癸酸（PFDA）和全氟十一烷酸（PFUnDA）是分别由9、10和11个碳组成的长链PFAS，它们对水生物种具有亚致死毒性。在此，我们综述了有关这些研究较少的长链PFAS在鱼类中的环境归宿和生态毒理学的数据。本研究的目的是：（1）汇编文献以比较PFNA、PFDA或PFUnDA扰乱的生理或分子信号通路；（2）使用基因本体计算方法揭示长链PFAS的潜在生物标志物和毒性途径，以阐明其作用机制。研究表明，PFAS对鱼类有一系列影响，包括发育问题、基因表达变化和行为改变。基于我们的综述，与PFDA和PFUnDA相比，PFNA在鱼类中的研究更为频繁；然而，较长链的PFAS被认为具有更大的毒性。基于计算方法，受PFNA影响的显著途径包括胰岛素信号传导["胰岛素 -> CEBPA/CTNNB/FOXA/FOXO", "胰岛素 -> STAT表达靶点"]、免疫系统信号传导["TNF -> STAT表达靶点", "IL6表达靶点", "IL2表达靶点"]以及生长激素/催乳素信号传导["GH1/PRLR表达靶点", "PRL/GHR -> STAT表达靶点", "PRL/PRLR表达靶点"]。一些与胆固醇代谢相关的转录本也受到PFNA的影响。本综述总结了目前关于PFNA、PFDA和PFUnDA在硬骨鱼中的分布、归宿和生态毒理学的知识，强调了潜在的生理和分子反应，这可能有助于在未来研究中评估长链PFAS的毒性。
