A Mixture of Persistent Organic Pollutants and Perfluorooctanesulfonic Acid Induces Similar Behavioural Responses, but Different Gene Expression Profiles in Zebrafish Larvae

Abstract

Persistent organic pollutants (POPs) are widespread in the environment and some may be neurotoxic. As we are exposed to complex mixtures of POPs, we aimed to investigate how a POP mixture based on Scandinavian human blood data affects behaviour and neurodevelopment during early life in zebrafish. Embryos/larvae were exposed to a series of sub-lethal doses and behaviour was examined at 96 h post fertilization (hpf). In order to determine the sensitivity window to the POP mixture, exposure models of 6 to 48 and 48 to 96 hpf were used. The expression of genes related to neurological development was also assessed. Results indicate that the POP mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf. This behavioural effect was associated with the perfluorinated compounds, and more specifically with perfluorooctanesulfonic acid (PFOS). The expression of genes related to the stress response, GABAergic, dopaminergic, histaminergic, serotoninergic, cholinergic systems and neuronal maintenance, were altered. However, there was little overlap in those genes that were significantly altered by the POP mixture and PFOS. Our findings show that the POP mixture and PFOS can have a similar effect on behaviour, yet alter the expression of genes relevant to neurological development differently.

Evaluation of Developmental Toxicity, Developmental Neurotoxicity, and Tissue Dose in Zebrafish Exposed to GenX and Other PFAS

“…However, although the pattern of the hyperactivity was identical across studies for PFOS with observed hyperactivity in the L1, L2, and D1 periods, it varied following exposure to PFHxS, where elevated locomotor activity was observed in the L1, L2, and D1 periods in Study 1 and the L2, D1, and D2 periods in Study 3. Regardless, in line with previously published work (Huang et al 2010;Khezri et al 2017;Spulber et al 2014), exposure to nonteratogenic concentrations of PFOS or PFHxS consistently triggered behavioral hyperactivity. Although more work is needed to understand the biological relevance of disparate xenobiotic-induced locomotor activity phenotypes, this represents a powerful approach for grouping chemicals based on shared toxicity phenotypes.…”

“…Compared with previously reported morphological and behavioral effects following exposure to PFBS, PFHxS, PFOS, or PFHxA (summarized in Table 5) (Hagenaars et al 2011;Huang et al 2010;Jantzen et al 2016;Khezri et al 2017;Padilla et al 2012;Spulber et al 2014;Truong et al 2014;Ulhaq et al 2013aUlhaq et al , 2013b, this study expanded our understanding of aliphatic PFAS toxicity to include data on PFPeS and PFHpS for the first time and reported novel results for PFHxA and PFHxS. Although not systematically designed to test a specific PFAS R-group (i.e., sulfonic or carboxylic acids), Ulhaq et al (2013a) tested 4-, 8-, 9-, and 10-carbon carboxylic acid aliphatic PFAS and 4-and 8-carbon sulfonic acid aliphatic PFAS in a zebrafish developmental toxicity assay and proposed the idea that carbon chain length may be a determinant of PFAS toxicity in zebrafish.…”

“…Another key area that needs to be explored is the mechanism(s) by which PFAS cause locomotor hyperactivity in zebrafish. Last, humans and wildlife are exposed to a complex mixture of PFAS (Boiteux et al 2016;Gebbink et al 2017;Strynar et al 2015), many of which may cause additive or synergistic disruption of neurodevelopmental signaling pathways (Khezri et al 2017). Future research should consider testing groups of related PFAS in environmentally relevant mixtures.…”

“…The developmental toxicity and developmental neurotoxicity of a subset of PFAS, such as PFOS and PFOA, have been previously evaluated in zebrafish (Hagenaars et al 2011;Huang et al 2010;Jantzen et al 2016; Khezri et al 2017;Spulber et al 2014;Ulhaq et al 2013aUlhaq et al , 2013b. PFOS exposure results in failed swim bladder inflation, abnormal ventroflexion of the tail (Hagenaars et al 2011;Huang et al 2010;Jantzen et al 2016;Ulhaq et al 2013a), and hyperactivity (Hurley et al 2018;Khezri et al 2017;Spulber et al 2014), whereas results for PFOA exposures are quite mixed for both developmental toxicity and behavior (Hagenaars et al 2011;Huang et al 2010;Jantzen et al 2016;Khezri et al 2017;Padilla et al 2012;Truong et al 2014;Ulhaq et al 2013aUlhaq et al , 2013b. However, because replacement PFAS such as GenX and ADONA are detected in the environment yet lack adequate data on their potential toxicity, the goal of this study was to assess the developmental toxicity, developmental neurotoxicity, and tissue doses of multiple aliphatic PFAS (e.g., PFOS, PFOA, PFHxS, and PFHxA), several emerging replacement PFAS (e.g., GenX and ADONA), and a polymer production by-product [e.g., perfluoro-3,6-dioxa-4-methyl-7-octene-1-sulfonic acid (PFESA1)] in parallel, using zebrafish as a test organism.…”

Sand Goby—An Ecologically Relevant Species for Behavioural Ecotoxicology

“…Several studies have reported that analysis of the swimming activity of larval stages of fish could provide predictions of mechanisms of action of unknown or less known compounds [13][14][15][16][17]. Behavioural studies using automatic video tracking systems have been shown to be successful for toxicity screening of different contaminants, like endocrine disrupting chemicals (EDCs), nanoparticles and metals [18,19], including complex mixtures [20][21][22]. Increasing recognition and use of behavioural endpoints in ecotoxicological studies is promoting interest for inclusion of behavioural effects as an alternative for lethal endpoints in environmental hazard assessment [12,23,24].…”