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Assessing developmental toxicity and transcriptomic responses to two per- and polyfluoroalkyl sulfonic acid (PFSA) exposures in the mummichog.
Citation:
Rericha, Y., T. Burke, H. Schrader, M. Francoeur, C. Heyder, K. Wells, L. Mills, N. McNabb, C. Lavelle, AND B. Clark. Assessing developmental toxicity and transcriptomic responses to two per- and polyfluoroalkyl sulfonic acid (PFSA) exposures in the mummichog. 29th NAC SETAC Annual Meeting 2023, Amherst, MA, June 20 - 21, 2023.
Impact/Purpose:
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and some cause adverse health effects, however, PFAS modes of action and hazards posed to fish populations are not well understood. This presentation describes experiments that contribute to our knowledge of the ecological hazard of PFAS though the integration of molecular events and organismal effects, which can inform population level impacts. In the present study, we conducted aqueous developmental exposures of mummichog (Fundulus heteroclitus) to two PFAS, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS), and assessed transcriptional, morphological, and behavioral changes early in development. Findings demonstrate the importance of an integrative 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 species.
Description:
Per- and polyfluoroalkyl substances (PFAS) are a ubiquitously detected chemical class that poses significant environmental health concerns. Perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS) are persistent in the environment and associated with adverse health effects. The hazards and modes of action by which individual PFAS cause adverse outcomes for fish populations are yet to be fully characterized. Therefore, we conducted embryo larval assays and transcriptomics using mummichogs (Fundulus heteroclitus, Atlantic killifish). Mummichogs are an important ecological model, amenable to early morphological and behavioral phenotyping and have a well-annotated genome. Embryos were aqueously exposed to PFHxS or PFOS (0, 1, 10, and 100 µM) for 6 days, beginning one day post fertilization (dpf). RNA sequencing (Novogene; Novaseq platform) was conducted at 3 or 4 dpf and at 10 dpf. Following exposures, embryos were assessed for morphology, heart rate, hatching, growth, swim bladder development, and behavior (10-30 dpf). Initial analysis revealed that exposure to 10 and 100 µM PFHxS induced robust gene expression changes at 3 dpf, while only 1 µM did so at 10 dpf. PFOS exposures elicited few transcriptional changes at 4 dpf but numerous differentially expressed genes at 10 dpf. Biological processes related to metabolic processes, ion transport, and DNA replication were among the most significantly enriched following PFOS exposures, while lipid transport and localization were enriched by PFHxS. At 10 dpf and subsequent timepoints, PFHxS and PFOS exposures induced limited developmental effects; mortality, heart rate, growth, and swim bladder development were not significantly affected. PFHxS exposures caused an increase in incidence of abnormal heart phenotypes (9%, 24%, and 26% compared to 3% in controls), including offset heart chambers and elongated sinus venosus. While morphological effects were limited, there were subtle behavior effects. PFOS (10 and 100 µM) exposures induced abnormal acceleration behavior during the dark period of a light/dark assay, and PFHxS exposures altered behavior during light/dark transition periods. Incidence of heart-specific phenotypes and abnormal behavior following PFAS exposures concur with previous studies in the literature, with mostly freshwater fish species. However, our lack of gross morphological effects at these concentrations is dissimilar to many studies, suggesting that investigation of sensitivity differences in mummichogs is warranted. Our findings and ongoing multi-omic studies will contribute to understanding of PFAS hazards, elucidate modes of action, connect molecular events to organismal outcomes, and inform efforts to predict population effects.
