Exposure of C. elegans eggs to a glyphosate-containing herbicide leads to abnormal neuronal morphology

Abstract

Recent data demonstrate that chronic exposure of Caenorhabditis elegans (C. elegans) to a high-use glyphosate-containing herbicide, Touchdown (TD), potentially damages the adult nervous system. It is unknown, however, whether unhatched worms exposed to TD during the egg stage show abnormal neurodevelopment post-hatching. Therefore, we investigated whether early treatment with TD leads to aberrant neuronal or neurite development in C. elegans. Studies were completed in three different worm strains with green fluorescent protein (GFP)-tagged neurons to facilitate visual neuronal assessment. Initially, eggs from C. elegans with all neurons tagged with GFP were chronically exposed to TD. Visual inspection suggested decreased neurite projections associated with ventral nerve cord neurons. Data analysis showed a statistically significant decrease in overall green pixel numbers at the fourth larval (L4) stage (*p < 0.05). We further investigated whether specific neuronal populations were preferentially vulnerable to TD by treating eggs from worms that had all dopaminergic (DAergic) or γ-aminobutyric acid (GABAergic) neurons tagged with GFP. As before, green pixel number associated with these discrete neuronal populations was analyzed at multiple larval stages. Data analysis indicated statistically significant decreases in pixel number associated with DAergic, but not GABAergic, neurons (***p< 0.001) at all larval stages. Finally, statistically significant decreases (at the first larval stage, L1) or increases (at the fourth larval stage, L4) in superoxide levels, a developmental signaling molecule, were detected (*p < 0.05). These data suggest that early exposure to TD may impair neuronal development, perhaps through superoxide perturbation. Since toxic insults during development may late render individuals more vulnerable to neurodegenerative diseases in adulthood, these studies provide some of the first evidence in this model organism that early exposure to TD may adversely affect the developing nervous system.

Re-registration Challenges of Glyphosate in the European Union

“…It has also been shown to serve as a source of phosphorous for algae at low concentrations (Klátyik et al, 2017b;Wang et al, 2017), and therefore, to potentially induce algal bloom (Drzyzga and Lipok, 2017). Formulated glyphosate-based herbicides, Touchdown R and Roundup R caused neurotoxicity (McVey et al, 2016) as well as locomotion and fertility inhibition (García-Espiñeira et al, 2018) on the nematode Caenorhabditis elegans. Following the results of the late Andrés Carrasco and his research group (Paganelli et al, 2010;Carrasco, 2013), recent findings in environmental toxicology of glyphosate and its formulated products include its revealed toxicity on amphibian species (Mann et al, 2009;Relyea and Jones, 2009;Meza-Joya et al, 2013;Wagner et al, 2013;Henao Muñoz et al, 2015;Baier et al, 2016a,b), on mollusks (Conners and Black, 2004) and on earthworms (Zaller et al, 2014;Gaupp-Berghausen et al, 2015).…”

Recent advances in understanding/assessing toxicity to the epigenome

“…Additionally, C. elegans has a transparent body that makes microscopic imaging of tissues and labeled proteins much easier than in mammals. For example, C. elegans expressing GFP-tagged neuronal populations (pan, dopaminergic, or GABAergic) were exposed to the herbicide glyphosate and the effect upon specific populations of neurons was determined 17 . In this study, dopaminergic neurons were more sensitive than GABAergic neurons to glyphosate exposure.…”

Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota

“…However, current emerging evidence suggests that glyphosate or GBH such as Roundup, can adversely affect mammalian biology via multiple mechanisms 5 – 8 . Several studies have also suggested the possible link between GBHs exposure and abnormality in neurodevelopment 9 , 10 . Among those mechanisms, it has been reported that GBHs exposure can alter the microbiota in honeybees, rats and other animals 11 , 12 and recently a shotgun metagenomic approach revealed that glyphosate alters the gut microbiome of Sprague–Dawley (SD) rats by inhibiting the shikimate pathway 13 .…”