Molecular Basis for Endocrine Disruption by Pesticides Targeting Aromatase and Estrogen Receptor

Chao Zhang,Alessandra Magistrato,Angelo Spinello,Silvia Bianchi,Giovanna Di Nardo,Tiziana Schilirò,Marta Gea,Gianfranco Gilardi

doi:10.3390/ijerph17165664

Abstract

The intensive use of pesticides has led to their increasing presence in water, soil, and agricultural products. Mounting evidence indicates that some pesticides may be endocrine disrupting chemicals (EDCs), being therefore harmful for the human health and the environment. In this study, three pesticides, glyphosate, thiacloprid, and imidacloprid, were tested for their ability to interfere with estrogen biosynthesis and/or signaling, to evaluate their potential action as EDCs. Among the tested compounds, only glyphosate inhibited aromatase activity (up to 30%) via a non-competitive inhibition or a mixed inhibition mechanism depending on the concentration applied. Then, the ability of the three pesticides to induce an estrogenic activity was tested in MELN cells. When compared to 17β-estradiol, thiacloprid and imidacloprid induced an estrogenic activity at the highest concentrations tested with a relative potency of 5.4 × 10−10 and 3.7 × 10−9, respectively. Molecular dynamics and docking simulations predicted the potential binding sites and the binding mode of the three pesticides on the structure of the two key targets, providing a rational for their mechanism as EDCs. The results demonstrate that the three pesticides are potential EDCs as glyphosate acts as an aromatase inhibitor, whereas imidacloprid and thiacloprid can interfere with estrogen induced signaling.

Highlights

Under the modern lifestyle, humans are exposed to various chemicals such as pesticide residuals in fruits and vegetables, antibiotics in meat and milk, preservatives in cosmetics and personal care products [1,2]
In order to study the effect of pesticide compounds on aromatase activity, a direct competitive estrone ELISA was performed using the purified cytochrome P450 reductase (CPR), as an electron donor from NADPH, and aromatase
The aromatase activity was evaluated by measuring the estrone production in the absence and presence of three different concentrations of pesticides (0.5, 1, and 5 μM)

Summary

Introduction

Humans are exposed to various chemicals such as pesticide residuals in fruits and vegetables, antibiotics in meat and milk, preservatives in cosmetics and personal care products [1,2]. These chemicals are usually in low doses and may not have a short term significant impact on the human body, but they can cause long term damages to health [3]. The compelling need of high food crop increasingly demands the use of chemicals This results in the extensive applications of millions of tons of pesticides every year [9,10].

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Conclusion