title: Mitochondrial Dysfunction, Disruption of F-Actin Polymerization, and Transcriptomic Alterations in Zebrafish Larvae Exposed to Trichloroethylene.
abstract: Trichloroethylene (TCE) is primarily used as an industrial degreasing agent and has been in use since the 1940s. TCE is released into the soil, surface, and groundwater. From an environmental and regulatory standpoint, more than half of Superfund hazardous waste sites on the National Priority List are contaminated with TCE. Occupational exposure to TCE occurs primarily via inhalation, while environmental TCE exposure also occurs through ingestion of contaminated drinking water. Current literature links TCE exposure to various adverse health effects including cardiovascular toxicity. Current studies aiming to address developmental cardiovascular toxicity utilized rodent and avian models, with the majority of studies using relatively higher parts per million (mg/L) doses. In this study, to further investigate developmental cardiotoxicity of TCE, zebrafish embryos were treated with 0, 10, 100, or 500 parts per billion (ppb; μg/L) TCE during embryogenesis and/or through early larval stages. After the appropriate exposure period, angiogenesis, F-actin, and mitochondrial function were assessed. A significant dose-response decrease in angiogenesis, F-actin, and mitochondrial function was observed. To further complement this data, a transcriptomic profile of zebrafish larvae was completed to identify gene alterations associated with the 10 ppb TCE exposure. Results from the transcriptomic data revealed that embryonic TCE exposure caused significant changes in genes associated with cardiovascular disease, cancer, and organismal injury and abnormalities with a number of targets in the FAK signaling pathway. Overall, results from our study support TCE as a developmental cardiovascular toxicant, provide molecular targets and pathways for investigation in future studies, and indicate a need for continued priority for environmental regulation.
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Wirbisky
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Nur P
authors.initials: NP
authors.lastname: Damayanti
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Cecon T
authors.initials: CT
authors.lastname: Mahapatra
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Sepúlveda
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Irudayaraj
authors.affiliation: School of Health Sciences, ‡Agricultural and Biological Engineering, §Department of Forestry and Natural Resources, ∥Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Freeman
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000737:chemistry*; D000818:Animals; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D023382:Toxicity Tests, Acute; D059467:Transcriptome / Q000187:drug effects; D014241:Trichloroethylene / Q000737:chemistry* / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000737:chemistry* / Q000633:toxicity; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000199:Actins; D014874:Water Pollutants, Chemical; D014241:Trichloroethylene; D051416:Focal Adhesion Protein-Tyrosine Kinases