Abstract
Glyphosate is found in a large array of non-selective herbicides such as Roundup® (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate-based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology. In the present study, relatively low doses of glyphosate (5mgkg-1 d-1 ), Roundup® (5mgkg-1 d-1 glyphosate equivalent), or vehicle were administered by ingestion to Sprague-Dawley rats from gestational day (GD) 10 to postpartum day (PD)22. The treatments significantly altered licking behaviour toward pups between PD2 and PD6. We also show in the dams at PD22 that Roundup exposure affected the maturation of doublecortin-immunoreactive new neurones in the dorsal dentate gyrus of the hippocampus of the mother. In addition, the expression of synaptophysin was up-regulated by glyphosate in the dorsal and ventral dentate gyrus and CA3 regions of the hippocampus, and down-regulated in the cingulate gyrus. Although a direct effect of glyphosate alone or its formulation on the central nervous system is currently not clear, we show that gut microbiota is significantly altered by the exposure to the pesticides, with significant alteration of the phyla Bacteroidetes and Firmicutes. This is the first study to provide evidence that glyphosate alone or in formulation (Roundup) differentially affects maternal behaviour and modulates neuroplasticity and gut microbiota in the mother.
Highlights
Glyphosate (N-phosphonomethyl-glycine) is the active compound found in over 750 broad-spectrum herbicides and is widely used across the world 1
In parallel to brain and behavior analysis, we investigated whether Glyphosate alone or in formulation could affect the gut microbiota and/or modulate plasma concentration of several cations to affect neuroplasticity in the dam
Synaptic plasticity in the hippocampus Findings of the present study show that peripartum exposure to Glyphosate and Roundup increased synaptophysin expression in the dorsal region of the dentate gyrus and interestingly, decreased synaptophysin expression in the cingulate gyrus, an area of the medial prefrontal cortex
Summary
Glyphosate (N-phosphonomethyl-glycine) is the active compound found in over 750 broad-spectrum herbicides and is widely used across the world 1. Glyphosate inhibits the 5-enolpyruvyl shikimate-3-phophate synthase (EPSPS), a key enzyme in the shikimate pathway [3,4]. This metabolic pathway is required for the biosynthesis of aromatic amino acids (tryptophan, tyrosine and phenylalanine) in plants, as well as in bacteria and fungi. Because this pathway is absent in vertebrates, Glyphosate was considered safe for animals and humans [3,5]. The debate on the safety of Glyphosate and Glyphosate-based herbicide in term of carcinogenicity is currently open [14,15,16,17]
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