Glyphosate‐based herbicide induces long‐lasting impairment in neuronal and glial differentiation

Abstract

Glyphosate-based herbicides (GBH) are among the most sold pesticides in the world.There are several formulations based on the active ingredient glyphosate (GLY) used along with other chemicals to improve the absorption and penetration in plants. The final composition of commercial GBH may modify GLY toxicological profile, potentially enhancing its neurotoxic properties. The developing nervous system is particularly susceptible to insults occurring during the early phases of development, and exposure to chemicals in this period may lead to persistent impairments on neurogenesis and differentiation. The aim of this study was to evaluate the long-lasting effects of a sub-cytotoxic concentration, 2.5 parts per million of GBH and GLY, on the differentiation of human neuroepithelial stem cells (NES) derived from induced pluripotent stem cells (iPSC). We treated NES cells with each compound and evaluated the effects on key cellular processes, such as proliferation and differentiation in daughter cells never directly exposed to the toxicants. We found that GBH induced a more immature neuronal profile associated to increased PAX6, NESTIN and DCX expression, and a shift in the differentiation process toward glial cell fate at the expense of mature neurons, as shown by an increase in the glial markers GFAP, GLT1, GLAST and a decrease in MAP2. Such alterations were associated to dysregulation of key genes critically involved in neurogenesis, including PAX6, HES1, HES5, and DDK1.Altogether, the data indicate that subtoxic concentrations of GBH, but not of GLY, induce long-lasting impairments on the differentiation potential of NES cells.

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment

“…Bipyridine heterocycle herbicide paraquat relies on the transfer of high-energy electrons in its planar bicyclic structure from the mitochondrial electron transfer chain to molecular oxygen to produce toxic ROS, which can induce cognitive impairment through oxidative stress (54). The rest of the pesticides according to their structure also can be divided into organic chlorine, carbamate, and pyrethroid (55,56). There is no detailed report on whether the mechanism causing cognitive impairment is related to their respective special structures.…”

Poisoning Regulation, Research, Health, and the Environment: The Glyphosate-Based Herbicides Case in Canada

“…In comparison, 2,4-D sales, also among the main herbicides used in the country, were 14 times lower [ 25 ]. Several studies have shown the impacts of glyphosate and GBHs on health [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. For example, a meta-analysis by Zhang et al showed an increase of 41% in cancer risk for agricultural workers with the highest exposure to complete GBH formulations [ 37 ].…”

Integrated metabolomics and transcriptomics reveal glyphosate based‐herbicide induced reproductive toxicity through disturbing energy and nucleotide metabolism in mice testes

“…Recent studies have reported the detection of glyphosate and its major metabolite aminomethylphosphonic acid in the human body 4–6 . In addition, several reports have revealed that GBH caused non‐target toxic effects in aquatic life and mammals, such as reproductive toxicity, neurotoxicity, thyrotoxicity, intestinal toxicity, and hepatotoxicity 7–11 . Therefore, environmental pollution caused by the heavy use of GBH has aroused worldwide public health concern.…”