The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity

Saal, Frederick S. vom; Nagel, Susan C.; Coe, Benjamin; Angle, Brittany M.; Taylor, Julia A.

doi:10.1016/j.mce.2012.01.001

Cited by 397 publications

(232 citation statements)

References 146 publications

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“…The strong estrogens that supported MCF-7 cell proliferation at subnanomolar concentrations included 17β-estradiol (E2), diethylstilbestrol (DES) (17), and 17α-ethynylestradiol (EE2) (18). Estrogens with intermediate strength supported MCF-7 cell proliferation at 1-100 nM and included two representative industrial chemicals BPA and p-nonylphenol (PNP) (1,19). The isoflavone phytoestrogens genistein and daidzein, which require metabolic activation for their full-strength estrogenic actions (20), were weak estrogens that supported MCF-7 cell proliferation at 0.1-10 μM.…”

Section: Generation Of Computational Models Of Dose-dependent Transcrmentioning

confidence: 99%

“…T he endocrine disrupting chemicals (EDCs) are environmental pollutants that interfere with the endocrine system to disturb biological processes such as development, reproduction, and metabolism (1)(2)(3)(4). EDCs consist of a wide variety of manmade and natural compounds with highly diversified chemical structures (4).…”

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confidence: 99%

“…GSE50705). 1 To whom correspondence may be addressed. E-mail: tshioda@partners.org or kisselbacher@partners.org.…”

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confidence: 99%

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Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes

Shioda

Rosenthal

Coser

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Although biological effects of endocrine disrupting chemicals (EDCs) are often observed at unexpectedly low doses with occasional nonmonotonic dose-response characteristics, transcriptomewide profiles of sensitivities or dose-dependent behaviors of the EDC responsive genes have remained unexplored. Here, we describe expressome analysis for the comprehensive examination of dosedependent gene responses and its applications to characterize estrogen responsive genes in MCF-7 cells. Transcriptomes of MCF-7 cells exposed to varying concentrations of representative natural and xenobiotic estrogens for 48 h were determined by microarray and used for computational calculation of interpolated approximations of estimated transcriptomes for 300 doses uniformly distributed in log space for each chemical. The entire collection of these estimated transcriptomes, designated as the expressome, has provided unique opportunities to profile chemical-specific distributions of ligand sensitivities for large numbers of estrogen responsive genes, revealing that at low concentrations estrogens generally tended to suppress rather than to activate transcription. Gene ontology analysis demonstrated distinct functional enrichment between high-and low-sensitivity estrogen responsive genes, supporting the notion that a single EDC chemical can cause qualitatively distinct biological responses at different doses. Expressomal heatmap visualization of dose-dependent induction of Bisphenol A inducible genes showed a weak gene activation peak at a very low concentration range (ca. 0.1 nM) in addition to the main, strong gene activation peak at and above 100 nM. Thus, expressome analysis is a powerful approach to understanding the EDC dose-dependent dynamic changes in gene expression at the transcriptomal level, providing important information on the overall profiles of ligand sensitivities and nonmonotonic responses.

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Section: Generation Of Computational Models Of Dose-dependent Transcrmentioning

confidence: 99%

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confidence: 99%

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Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes

Shioda

Rosenthal

Coser

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The etiology of obesity involves numerous factors that can be defined as hereditary, congenital, social and cultural (Kopelman and Grace, 2004;Ogden et al, 2006). There is growing experimental and epidemiological evidence that fetal programming of genetic systems is a contributing factor in the recent global increase in adult obesity (Vom Saal et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

Andreoli

Stoker

Rossetti

et al. 2015

Molecular and Cellular Endocrinology

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A B S T R A C TThe absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis.Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance.Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

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“…Its effects on mammary glands,3 on brain and behavioral development,4, 5 as well as on metabolism and obesity,6 have been reported. Nevertheless, clear epidemiological evidence of any health effects in humans is still missing.…”

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confidence: 99%

Derivatization of bisphenol A and its analogues with pyridine‐3‐sulfonyl chloride: multivariate optimization and fragmentation patterns by liquid chromatography/Orbitrap mass spectrometry

Regueiro

Andreas

Wenzl

2015

Rapid Commun. Mass Spectrom.

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RationaleDue to the growing restrictions on the use of bisphenol A (BPA), several other bisphenols are gaining importance as substitutes for BPA in a variety of applications. There is, therefore, a real need for selective and sensitive methods based on mass spectrometry which will allow the human exposure to these new bisphenols to be assessed.MethodsDerivatization of BPA and its substitutes with pyridine‐3‐sulfonyl chloride is used to enhance the detection capability of bisphenols by electrospray ionization mass spectrometry. A multivariate experimental design, Box‐Behnken response surface, was used to evaluate the influence of the main variables potentially affecting the derivatization yield. Fragmentation patterns for all the derivatized bisphenols were acquired by high‐resolution/accurate‐mass Orbitrap mass spectrometry.ResultsTemperature and pH were identified as the most important factors affecting the derivatization yield of bisphenols. Fragmentation of the protonated molecules produced abundant analyte‐specific product ions. Most of the derivatized bisphenols showed significant improvements in their signal‐to‐noise ratios compared with the underivatized forms. The stability of these derivatives was demonstrated through several freeze/thaw cycles, short‐term room temperature and long‐term cold storage.ConclusionsDerivatization of BPA and its structural analogues with pyridine‐3‐sulfonyl chloride is proposed as a specific, sensitive, high‐throughput approach to their analysis by liquid chromatography coupled to electrospray ionization mass spectrometry. © 2015 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.

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The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity

Cited by 397 publications

References 146 publications

Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes

Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

Derivatization of bisphenol A and its analogues with pyridine‐3‐sulfonyl chloride: multivariate optimization and fragmentation patterns by liquid chromatography/Orbitrap mass spectrometry

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