NMR-Based toxicometabolomics of Yellowtail Snapper (Ocyurus chrysurus) embryos, as a relevant ecological receptor, exposed to perfluorooctane sulfonate (PFOS)

Perfluorooctane sulfonate (PFOS) is a widespread and persistent environmental contaminant associated with adverse health effects. While previous studies have explored PFOS toxicity in various model systems, little is known with respect to ecologically relevant vertebrates. The present study utilized high-resolution magic-angle spinning (HRMAS) NMR spectroscopy for metabolomic profiling of embryonic stages of Yellowtail Snapper ( Ocyurus chrysurus ), as an ecologically relevant marine fish species, exposed to PFOS. Significant changes metabolite levels in embryos exposed to sublethal concentrations of PFOS, compared to unexposed controls, were identifed. Of the 41 metabolites resolved by HRMAS NMR, 18 showed significantly altered levels with PFOS exposure. Elevated levels of established biomarkers of hepatocytes and neural cells indicate targeting of these cellular systems, while increased levels of the antioxidants suggest a role of oxidative stress. Increased trimethylamine-N-oxide specifically suggests upregulation of flavin-containing monooxygenases, as a phase I detoxification pathway. Increases in numerous metabolites associated with energy metabolism align with reprogramming of metabolism including shift to mitochondrial energy metabolism. Notably, an increase in N-acetyllysine is consistent with acetylation, as a previously shown post-translational regulatory mechanism for peroxisome proliferator-activated receptor (PPAR), as a recognized target of PFOS. Taken together, metabolic profiles enabled a systems-level model of PFOS toxicity in the species to be proposed, and demonstrate utility of HRMAS NMR with respect to early life stages of marine fish as ecological receptors. Moreover, these findings reveal phylogenetically distinct metabolic impacts of PFOS in O. chrysurus , and potential biomarkers for environmental monitoring and toxicological assessment of this widespread environmental contaminant.