Endocrine and physiological effects of linuron and S-metolachlor in zebrafish developing embryos

Quintaneiro, C.; Patrício, D.; Novais, Sara; Soares, A.M.V.M.; Monteiro, M.S.

http://hdl.handle.net/10400.8/13986

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Abstract(s)

Evaluation of the effects of linuron and S-metolachlor on apical, biochemical and transcriptional endpoints in zebrafish (Danio rerio) early life stages was the main purpose of this work. Embryos were exposed for 96h to a range of concentrations of each herbicide to determine lethal and sub-lethal effects on apical (e.g. malformations, hatching) and biochemical parameters (cholinesterase, ChE; catalase, CAT; glutathione S-transferase, GST; lipid peroxidation, LPO and lactate dehydrogenase, LDH). To evaluate endocrine disruption effects, embryos were exposed during 96h to 0.88mg/L linuron and 9.66mg/L S-metolachlor, isolated or in binary mixture. Expression of a suite of genes involved in HPT, HPG and HPA-axis was then assessed. Highest concentration of linuron (5.0mg/L) decreased hatching rate to 5% and 70.0mg/L S-metolachlor completely inhibited hatching, about 100%. Both herbicides impaired development by inducing several malformations (100% in 5.0mg/L linuron and 70.0mg/L S-metolachlor). Linuron only affected GST and CAT at concentrations of 0.25 and 0.0025mg/L, respectively. S-metolachlor induced GST (to 256%), inhibited ChE (to 61%) and LDH (to 60%) and reduced LPO levels (to 63%). Linuron isolated treatment seems to have an estrogenic mode of action due to the observed induction of vtg1. Exposure to S-metolachlor seems to interfere with steroidogenesis and with HPT and HPA-axis, since it has inhibited cyp19a2, TSHβ and CRH gene expression. In addition to vtg1 induction and CRH inhibition, herbicide combination also induced sox9b that has a role in regulation of sexual development in zebrafish. This study pointed out adverse effects of linuron and S-metolachlor, namely impairment of neurotransmission and energy production, induction of steroidogenesis, and interference with HPT and HPA-axis. These results contributed to elucidate modes of action of linuron and S-metolachlor in zebrafish embryo model. Furthermore, gene expression patterns obtained are indicative of endocrine disruption action of these herbicides.

Keywords

Alternative methods Endocrine disruption Fish embryo toxicity Neurotoxicity Oxidative stress Teratogenic effects

URI

http://hdl.handle.net/10400.8/13986

Citation

Quintaneiro C, Patrício D, Novais SC, Soares AMVM, Monteiro MS. Endocrine and physiological effects of linuron and S-metolachlor in zebrafish developing embryos. Sci Total Environ. 2017 May 15;586:390-400. doi: 10.1016/j.scitotenv.2016.11.153. Epub 2017 Feb 13. PMID: 28209406