title: Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup.
abstract: BACKGROUND
  Glyphosate, the active ingredient in Roundup formulations, is the most widely used herbicide worldwide, and as a result contaminates surface waters and has been detected in food residues, drinking water and human urine, raising concerns for potential environmental and human health impacts. Research has shown that glyphosate and Roundup can induce a broad range of biological effects in exposed organisms, particularly via generation of oxidative stress. However, there has been no comprehensive investigation of the global molecular mechanisms of toxicity of glyphosate and Roundup for any species. We aimed to characterise and compare the global mechanisms of toxicity of glyphosate and Roundup in the liver of brown trout (Salmo trutta), an ecologically and economically important vertebrate species, using RNA-seq on an Illumina HiSeq 2500 platform. To do this, we exposed juvenile female brown trout to 0, 0.01, 0.5 and 10 mg/L of glyphosate and Roundup (glyphosate acid equivalent) for 14 days, and sequenced 6 replicate liver samples from each treatment.
  
  
  RESULTS
  We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. These included transcripts encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulating of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes.
  
  
  CONCLUSIONS
  These transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed at the lowest concentrations tested raises concerns for the potential toxicity of this herbicide to fish populations inhabiting contaminated rivers.
authors: Biosciences, College of Life & Environmental Sciences, Geoffrey Pope Building, University of Exeter, Exeter, EX4 4QD, UK. tu202@exeter.ac.uk.
authors: Tamsyn M
authors: TM
authors: Uren Webster
authors: Biosciences, College of Life & Environmental Sciences, Geoffrey Pope Building, University of Exeter, Exeter, EX4 4QD, UK. E.Santos@exeter.ac.uk.
authors: Eduarda M
authors: EM
authors: Santos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008099:Liver / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D012474:Salmon / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*; D014337:Trout / Q000235:genetics*; D014877:Water Pollution, Chemical; D000097797:Glyphosate
chemical_list: D000975:Antioxidants; D005998:Glycine; D006540:Herbicides; D000097797:Glyphosate
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