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Review
. 2021 Nov 22;22(22):12606.
doi: 10.3390/ijms222212606.

Pleiotropic Outcomes of Glyphosate Exposure: From Organ Damage to Effects on Inflammation, Cancer, Reproduction and Development

Marianna Marino  1 , Elena Mele  2 , Andrea Viggiano  1 , Stefania Lucia Nori  3 , Rosaria Meccariello  2 , Antonietta Santoro  1
Affiliations
Review

Pleiotropic Outcomes of Glyphosate Exposure: From Organ Damage to Effects on Inflammation, Cancer, Reproduction and Development

Marianna Marino et al. Int J Mol Sci. .

Abstract

Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an inhibitor of the shikimate pathway, which is absent in vertebrates. Due to this, international scientific authorities have long-considered glyphosate as a compound that has no or weak toxicity in humans. However, increasing evidence has highlighted the toxicity of glyphosate and its formulations in animals and human cells and tissues. Thus, despite the extension of the authorization of the use of glyphosate in Europe until 2022, several countries have begun to take precautionary measures to reduce its diffusion. Glyphosate has been detected in urine, blood and maternal milk and has been found to induce the generation of reactive oxygen species (ROS) and several cytotoxic and genotoxic effects in vitro and in animal models directly or indirectly through its metabolite, aminomethylphosphonic acid (AMPA). This review aims to summarize the more relevant findings on the biological effects and underlying molecular mechanisms of glyphosate, with a particular focus on glyphosate's potential to induce inflammation, DNA damage and alterations in gene expression profiles as well as adverse effects on reproduction and development.

Keywords: cancer; glyphosate toxicity; inflammation; reproduction and development.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The shikimate pathway in plants. The shikimate pathway converts phosphoenolpyruvate (PEP) and erythrose 4-phosphate (E 4-P) into chorismate, the precursor of three aromatic amino acids. Glyphosate inhibits the 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase enzyme, preventing this synthesis. DAHP: 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase; DHQ: 3-deidroquianate synthase; DHQ/SDH dehydratase: 3-dehydroquianate dehydratase; DHQ/SDH dehydrogenase: 3-dehydroquianate dehydrogenase; SK: shikimate kinase; CS: chorismate synthase.
Figure 2
Figure 2
Chemical structures of glyphosate and its co-genres: aminomethylphosphonic acid (AMPA), glycine and glutamic acid.
Figure 3
Figure 3
Scheme of the main exposure and contamination routes of glyphosate in humans. Image has been created with BioRender.com, accessed on 1 November 2021.
Figure 4
Figure 4
Schematic representation of glyphosate’s and glyphosate-based herbicide’s (GBHs) -induced effects on mammalian reproduction, fertility and development. ↓: decreased; ↑: increased.
Figure 5
Figure 5
Schematic overview of glyphosate- and GBHs-induced effects. Image has been created with BioRender.com, accessed on 1 November 2021.
See this image and copyright information in PMC

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