Effects and risk assessment of halogenated bisphenol A derivatives on human follicle stimulating hormone receptor: An interdisciplinary study.

Autor: Suteau V; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France., Zuzic L; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark., Hansen DH; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark., Kjølbye LR; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark., Sibilia P; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France., Gourdin L; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Briet C; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Thomas M; Poitiers University, Ecology & Biology of Interactions Laboratory, CNRS UMR 7285, INSERM CIC1402, IHES Research Group, Poitiers, France., Bourdeaud E; Poitiers University, Ecology & Biology of Interactions Laboratory, CNRS UMR 7285, INSERM CIC1402, IHES Research Group, Poitiers, France., Tricoire-Leignel H; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France., Schiøtt B; Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark., Carato P; Poitiers University, Ecology & Biology of Interactions Laboratory, CNRS UMR 7285, INSERM CIC1402, IHES Research Group, Poitiers, France., Rodien P; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Munier M; Angers University, MITOVASC, CarMe Team, CNRS UMR 6015, INSERM U1083, Angers, France; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France. Electronic address: mathilde.munier@univ-angers.fr.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Nov 05; Vol. 479, pp. 135619. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1016/j.jhazmat.2024.135619
Abstrakt: Halogenated bisphenol A (BPA) derivatives are produced during disinfection treatment of drinking water or are synthesized as flame retardants (TCBPA or TBBPA). BPA is considered as an endocrine disruptor especially on human follicle-stimulating hormone receptor (FSHR). Using a global experimental approach, we assessed the effect of halogenated BPA derivatives on FSHR activity and estimated the risk of halogenated BPA derivatives to the reproductive health of exposed populations. For the first time, we show that FSHR binds halogenated BPA derivatives, at 10 nM, a concentration lower than those requires to modulate the activity of nuclear receptors and/or steroidogenesis enzymes. Indeed, bioluminescence assays show that FSHR response is lowered up to 42.36 % in the presence of BPA, up to 32.79 % by chlorinated BPA derivatives and up to 27.04 % by brominated BPA derivatives, at non-cytotoxic concentrations and without modification of basal receptor activity. Moreover, molecular docking, molecular dynamics simulations, and site-directed mutagenesis experiments demonstrate that the halogenated BPA derivatives bind the FSHR transmembrane domain reducing the signal transduction efficiency which lowers the cellular cAMP production and in fine disrupts the physiological effect of FSH. The potential reproductive health risk of exposed individuals was estimated by comparing urinary concentrations (through a collection of human biomonitoring data) with the lowest effective concentrations derived from in vitro cell assays. Our results suggest a potentially high concern for the risk of inhibition of the FSHR pathway. This global approach based on FSHR activity could enable the rapid characterization of the toxicity of halogenated BPA derivatives (or other compounds) and assess the associated risk of exposure to these halogenated BPA derivatives.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zuzic Lorena reports equipment, drugs, or supplies was provided by Novo Nordisk Foundation. Zuzic Lorena reports financial support was provided by Lundbeck Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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