Metabolomic and Transcript Analysis Revealed a Sex-Specific Effect of Glyphosate in Zebrafish Liver.

Christian Giommi,Claudia Ladisa,Oliana Carnevali,Francesca Maradonna,Hamid Habibi

doi:10.3390/ijms23052724

Abstract

Glyphosate is a component of commonly used herbicides for controlling weeds in crops, gardens and municipal parks. There is increasing awareness that glyphosate-based herbicides, in addition to acting on plants, may also exert toxicity in wildlife and humans. In this study, male and female adult zebrafish were exposed to 700 µg/L of glyphosate (GLY), for 28 days. We used the metabolomic approach and UHPLC-ESI-MS to analyze liver samples to investigate the adverse effects of glyphosate on hepatic metabolism. The impact of GLY was found to be sex-specific. In female, GLY exposure affected purine metabolism by decreasing the levels of AMP, GMP and inosinic acid, consequently increasing uric acid levels with respect to the control (CTRL). Exposure to GLY also caused a decrease of UMP levels in the pyrimidine metabolism pathway. In male, GLY exposure decreased the aminoadipic acid within the lysine degradation pathway. Transcript analysis of genes involved in stress response, oxidative stress and the immune system were also performed. Results demonstrated an increased stress response in both sexes, as suggested by higher nr3c1 expression. However, the hsp70.2 transcript level was increased in female but decreased in male. The results demonstrated reduced sod1, sod2, and gpx1a in male following exposure to GLY, indicating an impaired oxidative stress response. At the same time, an increase in the cat transcript level in female was observed. mRNA levels of the pro-inflammatory interleukins litaf and cxcl8b.1 were increased in female. Taken together, the results provide evidence of disrupted nucleotide hepatic metabolism, increased stress inflammatory response in female and disruption of oxidative stress response in male.

Highlights

In both plants and microorganisms, the mechanism of action of the non-selective herbicide glyphosate (GLY), which is an amino phosphonic analogue of the amino acid glycine, relies on the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity, leading to reduced aromatic amino acid synthesis [1]
We used a metabolomic- and transcriptomic-based approach to investigate the toxicity of GLY alone and the equivalent
GLY can be detected in the urineofofthe humans of metabolism

Summary

Introduction

In both plants and microorganisms, the mechanism of action of the non-selective herbicide glyphosate (GLY), which is an amino phosphonic analogue of the amino acid glycine, relies on the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity, leading to reduced aromatic amino acid synthesis [1]. Glyphosate isopropylamine salt is used in combination with polyethoxylated tallow amine (POEA) which is the most utilized form of coadjutants. These formulations are sold under the trade name of Roundup® , in which the active ingredient is indicated as glyphosate acid equivalent (a.e.) and could be present at different concentrations. This herbicide is used extensively to eliminate weeds in conjunction with the use of genetically modified.

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Results

Conclusion