Androgenic activation, impairment of the monoaminergic system and altered behavior in zebrafish larvae

Journal Article (2021)


Science of the Total Environment





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  • Faria, Melissa

  • Prats, Eva

  • Rosas Ramírez, Jonathan Ricardo

  • Bellot, Marina

  • Bedrossiantz, Juliette

  • Pagano, Maria

  • Valls Brusco, Arnau

  • Gomez Canela, Cristian

  • Porta Pleite, Josep Maria

  • Mestres, Jordi

  • Garcia Reyero, Natalia

  • Faggio, Caterina

  • Gómez Oliván, Leobardo Manuel

  • Raldúa, Demetrio


Fenitrothion is an organophosphorus insecticide usually found in aquatic ecosystems at concentrations in the range of low ng/L. In this manuscript we show that 24 h exposure to environmental concentrations of fenitrothion, from ng/L to low μg/L, altered basal locomotor activity, visual-motor response and acoustic/vibrational escape response of zebrafish larvae. Furthermore, fenitrothion and expression of gap43a, gfap, atp2b1a, and mbp exhibited a significant non-monotonic concentration-response relationship. Once determined that environmental concentrations of fenitrothion were neurotoxic for zebrafish larvae, a computational analysis identified potential protein targets of this compound. Some of the predictions, including interactions with acetylcholinesterase, monoamine-oxidases and androgen receptor (AR), were experimentally validated. Binding to AR was the most suitable candidate for molecular initiating event, as indicated by both the up-regulation of cyp19a1b and sult2st3 and the non-monotonic relationship found between fenitrothion and the observed responses. Finally, when the integrity of the monoaminergic system was evaluated, altered levels of L-DOPA, DOPAC, HVA and 5-HIAA were found, as well as a significant up-regulation of slc18a2 expression at the lowest concentrations of fenitrothion. These data strongly suggest that concentrations of fenitrothion commonly found in aquatic ecosystems present a significant environmental risk for fish communities.



Author keywords

Neurotoxicity; Predicted target profile; Acetylcholinesterase inhibitor; Endocrine disruptors; Androgenic effects; Risk assessment

Scientific reference

M. Faria, E. Prats, J.R. Rosas, M. Bellot, J. Bedrossiantz, M. Pagano, A. Valls, C. Gomez-Canela, J.M. Porta, J. Mestres, N. Garcia-Reyero, C. Faggio, L.M. Gómez and D. Raldúa. Androgenic activation, impairment of the monoaminergic system and altered behavior in zebrafish larvae. Science of the Total Environment, 775: 145671, 2021.