You are here:
Assessing the effects of dietary exposure to PPAR agonists in mummichogs (Fundulus heteroclitus)
Citation:
Clark, B., D. Glinski, T. Ward, Matt Henderson, C. Lavelle, N. McNabb, S. Jayaraman, AND D. Nacci. Assessing the effects of dietary exposure to PPAR agonists in mummichogs (Fundulus heteroclitus). Society of Environmental Toxicology and Chemistry North America, 42nd Annual Meeting, NA, Virtual, November 14 - 18, 2021.
Impact/Purpose:
Some persistent compounds found in the environment cause toxicity through the peroxisome proliferator-activated receptor (PPAR) pathway, but these effects are not well understood in wild organisms. This presentation describes studies that will contribute to our understanding of the ecological risks associated with persistent pollutants that act through these toxic mechanisms. Here we fed fish two model chemicals that act through this pathway and assessed their growth, energy reserves, reproduction, and transcriptomic, proteomic, and metabolomic changes. The results demonstrate the value of integrating chemical, biological, and multi-omic endpoints to assess the effects and mechanisms of chemical stress in wild fish populations. Ultimately these studies will contribute to improved understanding by managers and scientists of mechanisms connecting human activities, ecological stressors, and ecosystem condition.
Description:
Evidence has grown that some persistent compounds found in the environment may have impacts on growth, reproduction, and metabolic homeostasis in mammals and fish that are mediated in part by interaction with the peroxisome proliferator-activated receptor (PPAR) pathway. To better understand the effects PPAR perturbation may have on populations of wild organisms, we exposed the estuarine fish Fundulus heteroclitus to the polybrominated diphenyl ether BDE99 and the human therapeutic clofibric acid (CLA) in diet. Although data are limited, both compounds interact with the PPARα pathway in fish and serve as model compounds for PPAR dysregulation. In the current study, wild-caught adult mummichog were individually tagged and placed in tanks receiving flowing seawater at 23 °C. Fish in four replicate tanks/treatment (2 male, 2 female/tank) were fed diets amended with acetone (control), BDE99 (75, 150, 375, or 750 ng/g fish ww/day), or CLA (80 µg/g fish ww/day) for 38 days. Weight and length were monitored throughout, and breeding was assessed by manual strip-spawning. On days 10 and 39, half of the fish were euthanized, and fish weight, length, and wet weight of gonad, liver, abdominal fat, and brain were recorded. Energetic reserves, as represented by changes in abdominal fat and liver mass, were affected in a dose-responsive manner by day 39. At day 10, fish in all BDE99 treatments were reproductive, but by day 39 all BDE- and CLA-treated fish exhibited dramatically reduced egg production compared to controls. Perturbations in the hepatic metabolome were also dose responsive, albeit more pronounced in females at the later timepoint after exposure to BDE99 and CLA. Assessment of transcriptomic, proteomic, and lipidomic responses and bioaccumulation is ongoing and will support a multi-omic approach to elucidate PPAR-mediated molecular toxicity pathways in fish. The results will also be extrapolated ecologically using bioenergetic and population models developed for this species. This work will support the development of Adverse Outcome Pathways and provide insight into outcomes of exposures to emerging contaminants of concern that are proposed to interact with PPAR in ecological species.
