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Investigating effects and mechanistic pathways of perfluoroalkyl substance (PFAS) toxicity in developing mummichog (Atlantic killifish) using multi-omics
Citation:
Rericha, Y., T. Burke, D. Glinski, C. Christen, H. Schrader, M. Francoeur, C. Heyder, K. Wells, A. Champagne, L. Mills, N. McNabb, W. Henderson, C. Lavelle, D. Nacci, AND B. Clark. Investigating effects and mechanistic pathways of perfluoroalkyl substance (PFAS) toxicity in developing mummichog (Atlantic killifish) using multi-omics. PRIMO22, Nantes, FRANCE, May 26 - 29, 2024.
Impact/Purpose:
Per- and polyfluoroalkyl substances (PFAS) are globally detected and shown to cause adverse health effects. However, PFAS modes of action and hazards posed to fish populations, particularly marine and estuarine, are not well understood. This presentation details a study that investigated effects of PFAS exposures across biological levels of organization (i.e., molecular to whole organism), specifically integrating transcriptomic and metabolomic data to gain insight into affected biological pathways. We conducted aqueous developmental exposures of mummichog (Fundulus heteroclitus) to two PFAS, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS), and assessed molecular, morphological, and behavioral changes early in development. Findings demonstrate the importance of an integrative and systems biology approach to our understanding of chemical mode of action and hazard assessment. Ultimately, this study will inform efforts to predict ecological hazard to fish populations and further elucidates PFAS mode of action in an ecologically relevant estuarine species.
Description:
Per- and polyfluoroalkyl substances (PFAS) are widespread, persistent chemicals associated with adverse health effects. However, mechanistic pathways underlying toxicity and hazards to wildlife, particularly estuarine and marine fish, are not fully characterized. We investigated developmental toxicity and multi-omic response after perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) exposures in mummichog (Fundulus heteroclitus). An ecologically important estuarine fish with a well-annotated genome, mummichogs are amenable to morphology, behavior, and ‘omics assessments. Embryos were nominally exposed to PFHxS or PFOS (1, 10, and 100 µM) from 1 to 6 days post-fertilization (dpf). RNA-seq was conducted at 3 or 4 and at 10 dpf, metabolomics at 10 dpf, and developmental endpoints (e.g., morphology, heart rate, growth, light/dark behavior) evaluated 10-30 dpf. ‘Omics analyses revealed similar and distinct responses. At 3 or 4 dpf, differentially expressed genes (DEGs) increased with concentration for both chemicals. At 10 dpf, 1 µM exposures induced the most DEGs, and PFOS elicited more than PFHxS. Metabolomic changes were also greater after PFOS exposure relative to PFHxS but greatest after 10 µM for both. Despite molecular changes, neither PFAS induced mortality or morphological effects, though additional data analysis is underway. Multi-omic data integration, alongside apical organismal effects, will contribute to understanding PFAS toxicity, elucidate underlying mechanistic pathways, and inform predictions of population-level impacts for marine species.
