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@article{1858732,
author = {Colville, Carly and Alcaraz, Alper James and Green, Derek and Park, Bradley and Xia, Jianguo and Soufan, Othman and Hruška, Pavel and Potěšil, David and Zdráhal, Zbyněk and Crump, Doug and Basu, Niladri and Hogan, Natacha and Hecker, Markus},
article_location = {NETHERLANDS},
article_number = {APR},
doi = {http://dx.doi.org/10.1016/j.scitotenv.2021.152747},
keywords = {Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways},
language = {eng},
issn = {0048-9697},
journal = {SCIENCE OF THE TOTAL ENVIRONMENT},
title = {Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)},
url = {http://www.sciencedirect.com/science/article/pii/S0048969721078268},
volume = {817},
year = {2022}
}
TY - JOUR
ID - 1858732
AU - 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
PY - 2022
TI - Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas)
JF - SCIENCE OF THE TOTAL ENVIRONMENT
VL - 817
IS - APR
SP - "152747"
EP - "152747"
PB - ELSEVIER
SN - 00489697
KW - Fathead minnow Fluoxetine Transcriptomics Proteomics Fecundity Toxicity pathways
UR - http://www.sciencedirect.com/science/article/pii/S0048969721078268
N2 - 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.
ER -
COLVILLE, Carly, Alper James ALCARAZ, Derek GREEN, Bradley PARK, Jianguo XIA, Othman SOUFAN, Pavel HRUŠKA, David POTĚŠIL, Zbyněk ZDRÁHAL, Doug CRUMP, Niladri BASU, Natacha HOGAN and Markus HECKER. Characterizing toxicity pathways of fluoxetine to predict adverse outcomes in adult fathead minnows (Pimephales promelas). \textit{SCIENCE OF THE TOTAL ENVIRONMENT}. NETHERLANDS: ELSEVIER, vol.~817, APR, p.~''152747'', 10 pp. ISSN~0048-9697. doi:10.1016/j.scitotenv.2021.152747. 2022.
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