Integrated multi-omics analysis reveals the underlying molecular mechanism for developmental neurotoxicity of perfluorooctanesulfonic acid in zebrafish.

Abstract

Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1-20μM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10μM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.