Marina Grimaldi

Université de Montpellier 1, Montpelhièr, Languedoc-Roussillon, France

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Publications (23)85.25 Total impact

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    ABSTRACT: Zebrafish is increasingly used as an animal model to study the effects of environmental nuclear receptors (NRs) ligands. As most of these compounds have only been tested on human NRs, it is necessary to measure their effects on zebrafish NRs. Estrogen receptors (ER) α and β and peroxysome proliferator activated receptor (PPAR) γ are main targets of environmental disrupting compounds (EDCs). In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα, zfERβ1 and zfERβ2. Only one isoform of PPARγ is expressed in both humans and zebrafish. In this review, we described reporter cell lines that we established to study the interaction of EDCs with human and zebrafish ERs and PPARγ. Using these cell lines, we observed that zfERs are thermo-sensitive while zfPPARγ is not. We also showed significant differences in the ability of environmental and synthetic ligands to modulate activation of zfERs and zfPPARγ in comparison to hERs and hPPARγ. Some environmental estrogens (bisphenol A, mycoestrogens) which are hER panagonists displayed greater potency for zfERα as compared to zfERβs. hERβ selective agonists (8βVE2, DPN, phytoestrogens) also displayed zfERα selectivity. Among hERα selective synthetic agonists, 16α-LE2 was the most zfERα selective compound. Almost all zfPPARγ environmental ligands (halogenated bisphenol A derivatives, phthalates, perfluorinated compounds) displayed similar affinity for human and zebrafish PPARγ while pharmaceutical hPPARγ agonists like thiazolidones are not recognized by zfPPARγ. Altogether, our studies show that all hERs and hPPARγ ligands do not control in a similar manner the transcriptional activity of zfERs and zfPPARγ and point out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
    Frontiers in Neuroscience 06/2015; 9. DOI:10.3389/fnins.2015.00212
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    ABSTRACT: Endocrine-disrupting chemicals (EDCs) are exogenous substances interfering with hormone biosynthesis, metabolism, or action, and consequently causing disturbances in the endocrine system. Various pathways are activated by EDCs, including interactions with nuclear receptors (NRs) which are primary targets of numerous environmental contaminants. The main NRs targeted by environmental contaminants are the estrogen (ER α, β) and the androgen (AR) receptors. ERs and AR have pleiotropic regulatory roles in a diverse range of tissues, notably in the mammary gland, the uterus and the prostate. Thus, dysfunctional ERs and AR signaling due to inappropriate exposure to environmental pollutants may lead to hormonal cancers and infertility. The pregnane X receptor (PXR) is also recognized by many environmental molecules. PXR has a protective role of the body through its ability to regulate proteins involved in the metabolism, the conjugation and the transport of many exogenous and endogenous compounds. However, the permanent activation of this receptor by xenobiotics may lead to premature drug metabolism, the formation and accumulation of toxic metabolites and defects in hormones homeostasis. The activity of other NRs can also be affected by environmental molecules. Compounds capable of inhibiting or activating the estrogen related (ERRγ), the thyroid hormone (TRα, β), the retinoid X receptors (RXRα, β, γ) and peroxisome proliferator-activated (PPAR α, γ) receptors have been identified and are highly suspected to promote developmental, reproductive, neurological, or metabolic diseases in humans and wildlife. In this review we provide an overview of reporter cell lines established to characterize the human NR activities of a large panel of EDCs including natural as well as industrial compounds such as pesticides, plasticizers, surfactants, flame retardants and cosmetics.
    Frontiers in Endocrinology 05/2015; 6. DOI:10.3389/fendo.2015.00062
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    ABSTRACT: Several human and fish bioassays have been designed to characterize the toxicity and the estrogenic activity of chemicals. However, their biotransformation capability (bio-activation/detoxification processes) is rarely reported, although this can influence the estrogenic potency of test compounds. The fate of two estrogenic chemicals, the UV filter benzophenone-2 (BP2) and the bisphenol A substitute bisphenol S (BPS) was deciphered in eight human and zebrafish in vitro cell models, encompassing hepatic and mammary cellular contexts. BP2 and BPS were metabolized into a variety of gluco- and sulfo-conjugated metabolites. Similar patterns of BP2 and BPS biotransformation were observed among zebrafish models (primary hepatocytes, ZFL and ZELH-zfER cell lines). Interestingly, metabolic patterns in zebrafish models and in the human hepatic cell line HepaRG shared many similarities, while biotransformation rates in cell lines widely used for estrogenicity testing (MELN and T47D-KBLuc) were quantitatively low and qualitatively different. This study provides new data on the comparative metabolism of BP2 and BPS in human and fish cellular models that will help characterize their metabolic capabilities, and underlines the relevance of using in vitro zebrafish-based bioassays when screening for endocrine disrupting chemicals.
    Environmental Science and Technology 02/2015; 49(6). DOI:10.1021/es505302c · 5.48 Impact Factor
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    ABSTRACT: The use of complementary and alternative medicine and herbal products, especially traditional Chinese medicines, is progressively rising for both adults and children. This increased use is based on the popular belief that these medicines are safe and harmless. In this report, we describe the results of a bedside-to-bench study that involved a short-statured 4-year-old boy with deficiencies in growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone due to an ectopic posterior pituitary gland and invisible pituitary stalk. Although the boy was given replacement therapy with hydrocortisone and L-thyroxin, the parents refused to treat him with growth hormone and consulted a naturopath who prescribed a traditional Chinese medicine (TCM) to stimulate the boy's growth. From the age of 20 months, the child's growth was regularly monitored while he was being treated with hydrocortisone, thyroxin, and the TCM. Over a 36-month period, the child's growth velocity accelerated (3 cm/year to 8 cm/year), his height increment substantially increased (-2 SD to -0.8 SD), and his bones matured. In the laboratory investigation, estrogen receptor (ER)alpha and ERbeta reporter cell lines were used to characterize the estrogenic activity of the TCM medicine and its 18 components, and the results established that the medicine and some of its components have estrogen receptor ERalpha and ERbeta selectivity and partial estrogen agonism. Partial estrogenic activity of the TCM was confirmed using whole-cell competitive binding, cell proliferation, and endogenous gene expression assays in the ERalpha-positive breast cancer cell lines. Although the presence of evidence is not always evidence of causality, we have concluded that this traditional Chinese medicine contains ingredients with estrogenic activity that can sustain bone growth and maturation without affecting other estrogen-dependent tissues.
    Reproductive Biology and Endocrinology 10/2014; 12(1):97. DOI:10.1186/1477-7827-12-97 · 2.41 Impact Factor
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    ABSTRACT: De nombreuses molécules environnementales agissent comme des perturbateurs endocriniens (PE) pouvant altérer le fonctionnement du système hormonal et ainsi avoir des effets néfastes sur la santé humaine. La plupart de ces composés, largement disséminés dans notre environnement, sont des produits de synthèse tels que les bisphénols, les phtalates, les parabènes ou encore les pesticides. Les PE ont pour cibles principales les récepteurs nucléaires d’hormones (RN), des facteurs de transcription qui en réponse à la liaison de petites molécules endogènes jouent un rôle essentiel toutes les fonctions métaboliques et physiologiques chez les métazoaires. Les PE sont ainsi susceptibles de perturber de nombreux processus de régulation et peuvent être à l’origine de troubles de la reproduction, du métabolisme ou même de cancers. Dans ce contexte, nous développons un projet visant à décrire l’action des polluants environnementaux sur les RN à l’échelle moléculaire. Pour cela nous utilisons une combinaison d’approches biochimique, cristallographique, biophysique et cellulaire. Ces différentes approches nous ont permis de mettre en évidence des modes de liaisons originaux des PEs qui peuvent beaucoup différer de ceux des ligands naturels ou pharmaceutiques. Nos études devraient ainsi permettre d’orienter la recherche et la synthèse de nouveaux composés industriels dépourvus de propriétés hormonales.
    Annales d Endocrinologie 10/2014; 75(s 5–6):248. DOI:10.1016/j.ando.2014.07.866 · 0.66 Impact Factor
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    ABSTRACT: Background: Individuals are exposed daily to environmental pollutants that may act as endocrine-disrupting chemicals (EDCs), causing a range of developmental, reproductive, metabolic, or neoplastic diseases. With their mostly hydrophobic pocket that serves as a docking site for endogenous and exogenous ligands, nuclear receptors (NRs) can be primary targets of small molecule environmental contaminants. However, most of these compounds are chemically unrelated to natural hormones, so their binding modes and associated hormonal activities are hardly predictable. Objectives: We conducted a correlative analysis of structural and functional data to gain insight into the mechanisms by which 12 members of representative families of pollutants bind to and activate the estrogen receptors ERα and ERβ. Methods: We used a battery of biochemical, structural, biophysical, and cell-based approaches to characterize the interaction between ERs and their environmental ligands. Results: Our study revealed that the chemically diverse compounds bound to ERs via varied sets of protein–ligand interactions, reflecting their differential activities, binding affinities, and specificities. We observed xenoestrogens binding to both ERs—with affinities ranging from subnanomolar to micromolar values—and acting in a subtype-dependent fashion as full agonists or partial agonists/antagonists by using different combinations of the activation functions 1 and 2 of ERα and ERβ. Conclusions: The precise characterization of the interactions between major environmental pollutants and two of their primary biological targets provides rational guidelines for the design of safer chemicals, and will increase the accuracy and usefulness of structure-based computational methods, allowing for activity prediction of chemicals in risk assessment. Citation: Delfosse V, Grimaldi M, Cavaillès V, Balaguer P, Bourguet W. 2014. Structural and functional profiling of environmental ligands for estrogen receptors. Environ Health Perspect 122:1306–1313; http://dx.doi.org/10.1289/ehp.1408453
    Environmental Health Perspectives 09/2014; 122(12). DOI:10.1289/ehp.1408453 · 7.03 Impact Factor
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    ABSTRACT: Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβ (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfERs isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hERs panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed amongst subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the differents zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
    Toxicology and Applied Pharmacology 08/2014; 280(1). DOI:10.1016/j.taap.2014.07.020 · 3.63 Impact Factor
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    ABSTRACT: Obesity has increased dramatically over the past decades, reaching epidemic proportions. The reasons are likely multifactorial. One of the suggested causes is the accelerated exposure to obesity-inducing chemicals (obesogens). However, out of the tens of thousands of industrial chemicals humans are exposed to, very few have been tested for their obesogenic potential, mostly due to the limited availability of appropriate in vivo screening models. In this study, we investigated whether two commonly used flame retardants, the halogenated bisphenol-A (BPA) analogs tetrabromobisphenol-A (TBBPA) and tetrachlorobisphenol-A (TCBPA), could act as obesogens using zebrafish larvae as an animal model in vivo. The effect of embryonic exposure to these chemicals on lipid accumulation was analyzed by Oil Red-O staining, and correlated to their capacity to activate human and zebrafish peroxisome proliferator-activated receptor gamma (PPARγ) in zebrafish and in reporter cell lines. Then, the metabolic fate of TBBPA and TCBPA in zebrafish larvae was analyzed by UV-HPLC. TBBPA and TCBPA were readily taken up by the fish embryo and both compounds were biotransformed to sulfate-conjugated metabolites. Both halogenated-BPAs, as well as TBBPA-sulfate induced lipid accumulation in zebrafish larvae and late-onset weight gain in juvenile zebrafish. These effects correlated to their capacity to act as zebrafish PPARγ agonists. Screening of chemicals for inherent obesogenic capacities through the zebrafish lipid accumulation model could facilitate prioritizing chemicals for further investigations in rodents, and ultimately, help protect humans from exposure to environmental obesogens.
    Toxicological Sciences 03/2014; 139(1). DOI:10.1093/toxsci/kfu036 · 4.48 Impact Factor
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    ABSTRACT: Many environmental endocrine disrupting compounds act as ligands for nuclear receptors. The human pregnane X receptor (hPXR), for instance, is activated by a variety of environmental ligands such as steroids, pharmaceutical drugs, pesticides, alkylphenols, polychlorinated biphenyls and polybromo diethylethers. Some of us have previously reported the occurrence of hPXR ligands in environmental samples but failed to identify them. The aim of this study was to test whether a PXR-affinity column, in which recombinant hPXR was immobilized on solid support, could help the purification of these chemicals. Using PXR ligands of different affinity (10 nM < EC50 < 10 μM), we demonstrated that the PXR-affinity preferentially column captured ligands with medium to high affinities (EC50 < 1 μM). Furthermore, by using the PXR-affinity column to analyze an environmental sample containing ERα, AhR, AR, and PXR activities, we show that (i) half of the PXR activity of the sample was due to compounds with medium to high affinity for PXR and (ii) PXR shared ligands with ERα, AR, and AhR. These findings demonstrate that the newly developed PXR-affinity column coupled to reporter cell lines represents a valuable tool for the characterization of the nature of PXR active compounds and should therefore guide and facilitate their further analysis. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
    Environmental Toxicology 02/2014; 29(2). DOI:10.1002/tox.20787 · 3.23 Impact Factor
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    ABSTRACT: Bisphenol-A (BPA) is one of the highest-volume chemicals produced worldwide and the widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Its estrogenic activity has been well documented in the last 15 years. In addition to estrogen receptors, BPA has been also shown to bind to and activate the estrogen-related receptor γ and pregnane X receptor and inhibit the androgen receptor. Halogenated BPAs were also shown to activate the peroxisome proliferator-activated receptor γ and inhibit thyroid hormone receptors. In this chapter, we review recent studies shedding light on the structural and molecular mechanisms by which BPA and its halogenated derivatives interfere with nuclear hormone receptor signaling. These data provide guidelines for the development of safer substitutes devoid of hormonal activity and may help environmental risk assessment.
    Vitamins & Hormones 01/2014; 94C:229-251. DOI:10.1016/B978-0-12-800095-3.00009-2 · 1.78 Impact Factor
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    ABSTRACT: Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.
    Environmental Science & Technology 12/2013; DOI:10.1021/es403899t · 5.48 Impact Factor
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    ABSTRACT: Bisphenols are a group of chemicals structurally similar to bisphenol-A (BPA) in current use as the primary raw material in the production of polycarbonate and epoxy resins. Some bisphenols are intended to replace BPA in several industrial applications. This is the case of bisphenol-S (BPS), which has an excellent stability at high temperature and resistance to sunlight. Studies on the endocrine properties of BPS have focused on its interaction with human estrogen receptor alpha (hERα), but information on its interaction with other nuclear receptors is scarce. The aim of this study was to investigate interactions of BPS, BPF, BPA and its halogenated derivatives, tetrachlorobisphenol A (TCBPA), and tetrabromobisphenol A (TBBPA), with human estrogen receptors (hERα and hERβ), androgen receptor (hAR), and pregnane X receptor (hPXR), using a panel of in vitro bioassays based on competitive binding to nuclear receptors (NRs), reporter gene expression, and cell proliferation assessment. BPS, BPF, and BPA efficiently activated both ERs, while TCBPA behaved as weak hERα agonist. Unlike BPF and BPA, BPS was more active in the hERβ versus hERα assay. BPF and BPA were full hAR antagonists (BPA>BPF), whereas BPA and BPS were weak hAR agonists. Only BPA, TCBPA, and TBBPA, were hPXR agonists (TCBPA>TBBPA>BPA). These findings provide evidence that BPA congeners and derivatives disrupt multiple NRs and may therefore interfere with the endocrine system. Hence, further research is needed to evaluate the potential endocrine-disrupting activity of putative BPA substitutes.
    Toxicology and Applied Pharmacology 05/2013; DOI:10.1016/j.taap.2013.05.015 · 3.63 Impact Factor
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    ABSTRACT: Complex mixtures of contaminants with potential adverse effects on human health and wildlife are found in the environment and in the food chain. These mixtures include numerous anthropogenic compounds of various origins and structures, which may behave as endocrine disruptors. Mixture's complexity is further enhanced by biotic and abiotic transformations. It is therefore necessary to develop new strategies allowing the identification of the structure of known, as well as unknown, nuclear receptor (NR) ligands present in complex matrices. We explored the possibility to use NR-based affinity columns to characterize the presence of bioactive molecules in environmental complex mixtures. Estrogen receptor α (ERα)-based affinity columns were used to trap and purify estrogenic substances present in surface sediment samples collected in a French river under mixed anthropogenic pressure. We combined biological, biochemical and analytical approaches to characterize the structure of ligands retained on columns and demonstrate the presence of known active molecules such as bisphenol A and octylphenol, but also of unexpected ERα ligands (n-butylparaben, hydroxyl-methyl-benzofuranone). High resolution mass spectrometry results demonstrate that ERα affinity columns can be used for the isolation, purification and identification of known as well as unknown estrogenic contaminants present in complex matrices.
    Environmental Science and Pollution Research 01/2013; DOI:10.1007/s11356-012-1458-z · 2.76 Impact Factor
  • Medecine sciences: M/S 01/2013; 29(1):14-7. DOI:10.1051/medsci/2013291004 · 0.52 Impact Factor
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    ABSTRACT: Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) α and β differ from that used by 17β-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17β-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor γ and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.
    Proceedings of the National Academy of Sciences 09/2012; 109(37):14930-14935. DOI:10.1073/pnas.1203574109 · 9.81 Impact Factor
  • PPTOX III International Conference, Environmental Stressors in the Developmental Origins of Disease: Evidence and Mechanisms; 05/2012
  • 6th Copenhagen Workshop on Endocrine Disrupters; 04/2012
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    ABSTRACT: The capability of the flame retardants tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) to activate peroxysome proliferator-activated receptors (PPARs) α, β, and γ and estrogen receptors (ERs) α and β has been recently investigated, but the activity of their biotransformation products and of their lower molecular weight analogues formed in the environment remains unexplored. The aim of this study was to investigate the relationship between the degree of halogenation of BPA analogues and their affinity and activity towards human PPARγ and ERs and to characterize active metabolites of major marketed halogenated bisphenols. The biological activity of all compounds was studied using reporter cell lines expressing these nuclear receptors (NRs). We used NR-based affinity columns to rapidly evaluate the binding affinity of halogenated bisphenols for PPARγ and ERs and to trap active metabolites of TBBPA and TCBPA formed in HepG2 cells. The agonistic potential of BPA analogs highly depends on their halogenation degree: the bulkier halogenated BPA analogs, the greater their capability to activate PPARγ. In addition, PPARγ-based affinity column, HGELN-PPARγ reporter cell line and crystallographic analysis clearly demonstrate that the sulfation pathway, usually considered as a detoxification process, leads for TBBPA and TCBPA, to the formation of sulfate conjugates which possess a residual PPARγ-binding activity. Our results highlight the effectiveness NR-based affinity columns to trap and characterize biologically active compounds from complex matrices. Polyhalogenated bisphenols, but also some of their metabolites, are potential disrupters of PPARγ activity.
    Toxicological Sciences 05/2011; 122(2):372-82. DOI:10.1093/toxsci/kfr132 · 4.48 Impact Factor
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    ABSTRACT: The occurrence of halogenated analogs of the xenoestrogen bisphenol A (BPA) has been recently demonstrated both in environmental and human samples. These analogs include brominated [e.g., tetrabromobisphenol A (TBBPA)] and chlorinated [e.g., tetrachlorobisphenol A (TCBPA)] bisphenols, which are both flame retardants. Because of their structural homology with BPA, such chemicals are candidate endocrine disruptors. However, their possible target(s) within the nuclear hormone receptor superfamily has remained unknown. We investigated whether BPA and its halogenated analogs could be ligands of estrogen receptors (ERs) and peroxisome proliferator-activated receptors (PPARs) and act as endocrine-disrupting chemicals. We studied the activity of compounds using reporter cell lines expressing ERs and PPARs. We measured the binding affinities to PPARγ by competitive binding assays with [3H]-rosiglitazone and investigated the impact of TBBPA and TCBPA on adipocyte differentiation using NIH3T3-L1 cells. Finally, we determined the binding mode of halogenated BPAs to PPARγ by X-ray crystallography. We observed that TBBPA and TCBPA are human, zebrafish, and Xenopus PPARγ ligands and determined the mechanism by which these chemicals bind to and activate PPARγ. We also found evidence that activation of ERα, ERβ, and PPARγ depends on the degree of halogenation in BPA analogs. We observed that the bulkier brominated BPA analogs, the greater their capability to activate PPARγ and the weaker their estrogenic potential. Our results strongly suggest that polyhalogenated bisphenols could function as obesogens by acting as agonists to disrupt physiological functions regulated by human or animal PPARγ.
    Environmental Health Perspectives 05/2011; 119(9):1227-32. DOI:10.1289/ehp.1003328 · 7.03 Impact Factor

Publication Stats

293 Citations
85.25 Total Impact Points

Institutions

  • 2013–2014
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 2010–2014
    • French Institute of Health and Medical Research
      • Montpellier Cancer Research Institute IRCM
      Lutetia Parisorum, Île-de-France, France
  • 2009–2014
    • Institut de Recherche en Cancerologie de Montpellier
      Montpelhièr, Languedoc-Roussillon, France