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Leveraging multi-omics to elucidate mechanistic pathways associated with developmental exposures to perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) in mummichog
Citation:
Rericha, Y., T. Burke, D. Glinski, H. Schrader, M. Francoeur, C. Heyder, K. Wells, L. Mills, N. McNabb, C. Lavelle, Matt Henderson, D. Nacci, AND B. Clark. Leveraging multi-omics to elucidate mechanistic pathways associated with developmental exposures to perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) in mummichog. SETAC North America Annual Meeting, Louisville, KY, November 12 - 16, 2023.
Impact/Purpose:
Many per- and polyfluoroalkyl substances (PFAS) are persistent and cause adverse health effects, but the affected mechanistic pathways and hazards to wild fish populations are not well understood. This presentation describes studies that deepen our understanding of the ecological hazard of PFAS through the integration of multi-omics molecular changes and organismal effects in a marine fish species. We conducted aqueous developmental exposures of mummichog (Fundulus heteroclitus) to two PFAS, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS), and assessed transcriptional, metabolomic, morphological, and behavioral changes during early life stages. Findings demonstrate the importance of an integrative multi-omics and systems biology approach to understand affected biological pathways, which can inform population level impacts. Ultimately, this study will inform efforts to predict ecological hazard to fish populations and further elucidate mechanistic pathways of PFAS toxicity.
Description:
Many per- and polyfluoroalkyl substances (PFAS) are highly persistent in the environment and have been associated with adverse health effects in a variety of species. However, the mechanistic pathways through which PFAS induce toxicity and the hazards posed to wild fish populations are not yet fully characterized. In this study, we assessed developmental toxicity and measured multi-omic endpoints in mummichogs (Fundulus heteroclitus, Atlantic killifish) exposed to perfluorohexane sulfonate (PFHxS) or perfluorooctane sulfonate (PFOS) to investigate the perturbed biological pathways underlying apical organismal effects. An important ecological model, mummichogs are an estuarine fish amenable to morphological and behavioral phenotyping and have a well-annotated genome. Mummichog embryos were aqueously exposed to PFHxS (1.0, 10, and 100 µM) or PFOS (0.93, 9.3, and 93 µM) from one day post fertilization (dpf) until 7 dpf. RNA sequencing (Novaseq platform; Novogene) was conducted at 3 or 4 dpf and at 10 dpf, and metabolomics profiling at 10 dpf. Additionally, developmental endpoints such as morphology, heart rate, growth, swim bladder development and larval light/dark behavior were evaluated between 10-30 dpf. Assessment of multi-omic endpoints preceding or coinciding with apical effects, will contribute to a holistic understanding of PFAS toxicity and the underlying mechanisms. RNA-seq data analysis revealed that exposure to 10 and 100 µM PFHxS induced robust gene expression changes at 3 dpf, and 1 µM at 10 dpf. PFOS exposures elicited fewer differentially expressed genes at 4 dpf compared to 10 dpf. Biological processes related to metabolism, ion transport, DNA replication, and lipid transport and localization were disrupted. Despite transcriptional changes, neither PFAS induced gross organismal-level effects. PFHxS caused a subtle increase in abnormal heart phenotypes at 10 dpf (9%, 24%, and 26% compared to 3% incidence in controls) and both chemical exposures led to subtle behavior effects at 24 dpf. Abnormal heart and behavior phenotypes concur with previous PFAS studies in freshwater fish species; the lack of gross morphological effects may warrant further investigation into sensitivity differences between species. Multi-omics integration is currently underway and will contribute to our understanding of PFAS ecotoxicity, elucidate modes of action leading to subtle organismal effects, and inform efforts to predict population-level impacts.
URLs/Downloads:
https://www.setac.org/discover-events/global-meetings/setac-north-america-44th-annual-meeting/general-info/important-dates.html