The bisphenol A metabolite MBP causes proteome alterations in male Cyprinodon variegatus fish characteristic of estrogenic endocrine disruption

Alexandre M Schönemann,Sandra Isabel Moreno Abril,Angel P Diz,Ricardo Beiras

doi:10.1016/j.envpol.2022.118936

Alexandre M Schönemann, Sandra Isabel Moreno Abril + Show 2 more

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https://doi.org/10.1016/j.envpol.2022.118936

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Journal: Environmental Pollution	Publication Date: Feb 3, 2022
Citations: 5	License type: cc-by

Affiliation: Universidade de Vigo

Abstract

The toxicological status of bisphenol A (BPA) is under strong debate. Whereas in vitro it is an agonist of the estrogen receptor with a potency ca. 105-fold lower than the natural female hormone estradiol, in vivo exposure causes only mild effects at concentration thresholds environmentally not relevant and inconsistent among species. By using a proteomic approach, shotgun liver proteome analysis, we show that 7-d exposure to 10 μg/L of the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), and not the same exposure to the parental molecule BPA, alters the liver proteome of male Cyprinodon variegatus fish. Different physiological and environmental conditions leading to biotransformation of BPA to MBP may partly explain the conflicting results so far reported for in vivo BPA exposures. The pattern of alteration induced by MBP is similar to that caused by estradiol, and indicative of estrogenic endocrine disruption. MBP enhanced ribosomal activity, protein synthesis and transport, with upregulation of 91% of the ribosome-related proteins, and 12 proteins whose expression is regulated by estrogen-responsive elements, including vitellogenin and zona pellucida. Whey acidic protein (WAP) was the protein most affected by MBP exposure (FC = 68). This result points at WAP as novel biomarker for xenoestrogens.

Highlights

Xenoestrogens are synthetic chemicals that bind to specific estrogen receptors (ER) and induce biological responses similar to those of estradiol, at concentrations generally 3 to 6 orders of magni tude higher (Witorsch, 2002)
The liver proteome profile of bisphenol A (BPA)-exposed C. variegatus adult males showed 21,325 peptide sequences, from which 3013 protein groups were identified and quantified. 81 of these proteins present statistically significant differences (p < 0.05) in abundance compared to those found in the solvent control (SC) samples
The liver proteome profile from the MBP-exposed adult males is composed by 24,360 peptide sequences, from which 2711 proteins could be identified; 2519 of them were common to those identified in the BPAexposed fish

Summary

Introduction

Xenoestrogens are synthetic chemicals that bind to specific estrogen receptors (ER) and induce biological responses similar to those of estradiol, at concentrations generally 3 to 6 orders of magni tude higher (Witorsch, 2002). In vitro tests, such as those using re combinant yeast, detect molecules that bind to ER, and with potential for estrogenic endocrine disruption (ED). Vitellogenin (VTG), a precursor protein of egg yolk, codified by a gene found to be regulated by ERE in fish (Teo et al, 1998), has been commonly used for in vivo detection of xenoestrogens. VTG synthesis in adult males or immature fish is a well-known biomarker of estrogenic ED (Cheek et al, 2001; Knoebl et al, 2004; Rose et al, 2002; Tyler et al, 1999)

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