Effects of Perfluorinated Alkyl Substances (PFAS) on Amphibian Body and Liver Conditions: Is Lipid Metabolism Being Perturbed throughout Metamorphosis?
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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引用次数: 0
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.
ToxicsChemical 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.