Effects of Perfluorinated Alkyl Substances (PFAS) on Amphibian Body and Liver Conditions: Is Lipid Metabolism Being Perturbed throughout Metamorphosis?

IF 3.9 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Toxics Pub Date : 2024-10-10 DOI:10.3390/toxics12100732
Anna Bushong, Maria Sepúlveda, Meredith Scherer, Abigail C Valachovic, C Melman Neill, Sophia Horn, Youn Choi, Linda S Lee, Priyanka Baloni, Tyler Hoskins
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Abstract

Per- and polyfluoroalkyl substances (PFAS) may interact with peroxisome proliferator activated receptors (PPARs) and alter lipid homeostasis. Using Xenopus laevis, we investigated the effect of PFAS on (a) lipid homeostasis and whether this correlated to changes in body and hepatic condition; (b) the expression of hepatic genes regulated by PPAR; and (c) the hepatic lipidome. We chronically exposed tadpoles to 0.5 µg/L of either PFOS, PFHxS, PFOA, PFHxA, a binary mixture of PFOS and PFHxS (0.5 µg/L of each), or a control, from NF stage 52 through metamorphic climax. Growth, development, and survival were not affected, but we detected a sex-specific decrease in body condition at NF 66 (6.8%) and in hepatic condition (16.6%) across metamorphic climax for male tadpoles exposed to PFOS. We observed weak evidence for the transient downregulation of apolipoprotein-V (apoa5) at NF 62 in tadpoles exposed to PFHxA. Acyl-CoA oxidase 1 (acox1) was downregulated only in males exposed to PFHxS (Ln(Fold Change) = -0.54). We detected PFAS-specific downregulation of structural glycerophospholipids, while semi-quantitative profiling detected the upregulation in numerous glycerophospholipids, sphingomyelins, and diglycerides. Overall, our findings indicate that PFAS can induce sex-specific effects that change across larval development and metamorphosis. We demonstrate that PFAS alter lipid metabolism at environmentally relevant concentrations through divergent mechanisms that may not be related to PPARs, with an absence of effects on body condition, demonstrating the need for more molecular studies to elucidate mechanisms of PFAS-induced lipid dysregulation in amphibians and in other taxa.

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全氟烷基物质 (PFAS) 对两栖动物身体和肝脏状况的影响:脂质代谢是否在整个变态过程中受到干扰?
全氟和多氟烷基物质(PFAS)可能会与过氧化物酶体增殖物激活受体(PPARs)相互作用并改变脂质稳态。我们利用爪蟾研究了 PFAS 对以下方面的影响:(a) 脂质稳态,以及这是否与身体和肝脏状况的变化相关;(b) 受 PPAR 调节的肝脏基因的表达;以及 (c) 肝脏脂质体。我们将蝌蚪长期暴露于 0.5 µg/L 的 PFOS、PFHxS、PFOA、PFHxA、PFOS 和 PFHxS 的二元混合物(每种均为 0.5 µg/L)或对照组中,从 NF 阶段 52 开始,直至变态高潮。雄性蝌蚪的生长、发育和存活率均未受到影响,但我们检测到,暴露于全氟辛烷磺酸的雄性蝌蚪在NF 66期的身体状况(6.8%)和肝脏状况(16.6%)在整个变态高潮期均出现了性别特异性下降。我们观察到暴露于全氟辛烷磺酸的蝌蚪在 NF 62 处脂蛋白-V(apoa5)短暂下调的微弱证据。酰基-CoA 氧化酶 1(acox1)仅在暴露于 PFHxS 的雄性蝌蚪中出现下调(折线变化率 Ln(Fold Change) = -0.54)。我们检测到结构性甘油磷脂的 PFAS 特异性下调,而半定量分析检测到许多甘油磷脂、鞘磷脂和二甘油酯的上调。总之,我们的研究结果表明,全氟辛烷磺酸可诱导性别特异性效应,并在幼虫发育和变态过程中发生变化。我们的研究表明,在环境相关浓度下,PFAS会通过不同的机制改变脂质代谢,这些机制可能与PPARs无关,但对身体状况没有影响,这表明需要进行更多的分子研究,以阐明PFAS诱导两栖动物和其他类群脂质失调的机制。
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
Toxics
Toxics Chemical Engineering-Chemical Health and Safety
CiteScore
4.50
自引率
10.90%
发文量
681
审稿时长
6 weeks
期刊介绍: The Journal accepts papers describing work that furthers our understanding of the exposure, effects, and risks of chemicals and materials in humans and the natural environment as well as approaches to assess and/or manage the toxicological and ecotoxicological risks of chemicals and materials. The journal covers a wide range of toxic substances, including metals, pesticides, pharmaceuticals, biocides, nanomaterials, and polymers such as micro- and mesoplastics. Toxics accepts papers covering: The occurrence, transport, and fate of chemicals and materials in different systems (e.g., food, air, water, soil); Exposure of humans and the environment to toxic chemicals and materials as well as modelling and experimental approaches for characterizing the exposure in, e.g., water, air, soil, food, and consumer products; Uptake, metabolism, and effects of chemicals and materials in a wide range of systems including in-vitro toxicological assays, aquatic and terrestrial organisms and ecosystems, model mammalian systems, and humans; Approaches to assess the risks of chemicals and materials to humans and the environment; Methodologies to eliminate or reduce the exposure of humans and the environment to toxic chemicals and materials.
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