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Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)


COLVILLE Carly ALCARAZ Alper James GREEN Derek PARK Bradley XIA Jianguo SOUFAN Othman HRUŠKA Pavel POTĚŠIL David ZDRÁHAL Zbyněk CRUMP Doug BASU Niladri HOGAN Natacha HECKER Markus

Year of publication 2022
Type Article in Periodical
MU Faculty or unit

Faculty of Science

Web fulltext
Keywords Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways
Description Current ecotoxicity testing programs are impeded as they predominantly rely on slow and expensive animal tests measuring adverse outcomes. Therefore, new approach methodologies (NAMs) increasingly involve short-term mechanistic assays that employ molecular endpoints to predict adverse outcomes of regulatory relevance. This study aimed to elucidate the application of NAMs in adult fathead minnows using fluoxetine (FLX) as a model compound. Fish were exposed to three FLX concentrations (measured: 2.42, 10.7, and 56.7 mu gL(-1)) and a control. After 96 h, molecular toxicity signatures were characterized using proteomics and transcriptomics analyses in livers and brains of a sub-set of fish. The remaining fish were sampled at 21 days and assessed for liver histopathology and morphometric measurements. Fecundity was monitored throughout the study. In the livers, 56.7 mu gL(-1) FLX caused enrichment of PPAR signaling in the proteome and fatty acid-related pathways in the transcriptome, potential upstream responses that led to lipid-type vacuolation of hepatocytes, observed via histopathology. Upregulated genes in the brain suggested alterations in serotonin-related signaling processes and reproductive behaviour, which may explain the observed signifi-cant decrease in fecundity. While the relationships between molecular responses and adverse outcomes remain complex, this research provided important insights into the mechanistic toxicity of FLX.
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