Profiling of bisphenol A and eight of its analogues on transcriptional activity via human nuclear receptors

Kojima, Hiroyuki; Takeuchi, Shinji; Sanoh, Seigo; Okuda, Kunio; Kawa, Shigeyuki; Uramaru, Naoto; Sugihara, Kazumi; Yoshinari, Kouichi

doi:10.1016/j.tox.2018.12.001

Cited by 108 publications

(70 citation statements)

References 60 publications

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“…Due to the endocrine-disrupting properties of BPA, much effort has been devoted to the development of analogs such as bisphenol F (BPF) and bisphenol S (BPS) ( Figure 3) in the hope that substitutes might be found without adverse activity. However, models both in vivo (Mu et al, 2018) and in vitro (Kojima et al, 2019) have shown that these analogs can still bind to estrogen receptors and give estrogenic responses on gene expression albeit with some differences in detailed mechanisms of action at a molecular level, (Li et al, 2018).…”

Section: Evidence For Endocrine Disrupting Properties Of Bpamentioning

confidence: 99%

Chemical components of plastics as endocrine disruptors: Overview and commentary

Darbre

2020

Birth Defects Research

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Bisphenol A and phthalate esters are used as additives in the manufacture of plastic materials, but their ability to leach out with age and heat has resulted in their becoming ubiquitous contaminants of the ecosystem including within human body tissues. Over recent years, these compounds have been shown to possess endocrine disrupting properties with an ability to interfere in the actions of many hormones and to contribute to human health problems. Much of the reported disruptive activity has been in relation to the action of estrogens, androgens, and thyroid hormones, and concerns have been raised for adverse consequences on female and male reproductive health, thyroid function, metabolic alterations, brain development/function, immune responses, and development of cancers in hormone-sensitive tissues. A recurring theme throughout seems to be that there are windows of susceptibility to exposure in utero and in early postnatal life, which may then result in disease in later life without any need for further exposure. This commentary highlights key issues in a historical context and raises questions regarding the many data gaps.

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Section: Evidence For Endocrine Disrupting Properties Of Bpamentioning

confidence: 99%

Chemical components of plastics as endocrine disruptors: Overview and commentary

Darbre

2020

Birth Defects Research

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“…Our data suggests that BPS may indeed be associated with less breast cancer risk when compared to BPA. It is worth noting that BPS has weaker estrogenic activity than BPA, suggesting that activity may be the driver of risk (Kojima et al 2019;Ng et al 2015;Rochester and Bolden 2015). In contrast, DES is a very strong estrogen and similarly drove a strong gland stiffness phenotype.…”

Section: Bpa Alternatives and The Importance Of Estrogenic Activitymentioning

confidence: 99%

“…The ability of BPA to act as an estrogen has raised concerns over these exposures, leading to its replacement in various commercial products. These BPA replacements have varying levels of estrogenic activity with compounds such as bisphenol AF having higher estrogenic activity than BPA and bisphenol S (BPS) having lower estrogenic activity (Kojima et al 2019;Ng et al 2015;Rochester and Bolden 2015).…”

Section: Introductionmentioning

confidence: 99%

In uteroestrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness

Wormsbaecher

Hindman

Avendano

et al. 2019

Preprint

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AbstractIn utero endocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Several lines of evidence indicate the stroma mediates endocrine disruption following early-life (or in utero) exposure. Herein, we utilized BPA as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Using RNA-seq transcriptional profiling of adult primary fibroblasts isolated from female mice exposed to BPA in utero, we identified deregulated genes associated with the extracellular matrix. Specifically, multiple collagen genes had increased expression in exposed mice. In line with the transcriptional data, collagen deposition is increased in adult BPA-exposed mice. We further demonstrate in vitro that fibroblasts exposed to BPA in utero remodel a collagen matrix, thereby decreasing permeability of the collagen matrix. These alterations to the mammary gland resulted in increased gland stiffness in the adult mice. Our data connects early life endocrine disruption to breast density. Interestingly, increased collagen deposition and gland stiffness were not observed in the developing glands of younger mice, suggesting risk factors for breast cancer continue to develop throughout life following these exposures. Finally, we assessed whether in utero exposure to two other endocrine disruptors, BPS and DES, also increase breast stiffness in adult mice. While DES increased breast stiffness, BPS did not, suggesting this BPA alternative may in fact pose less breast cancer risk than its predecessor. As breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically link endocrine disruptor exposures and molecular alterations to increased disease susceptibility in the gland.

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“…Thus, the potential effects of EDs on downstream gene expression are variable. Furthermore, many examples showing ED interactions with various NRs indicate that one compound may simultaneously interfere with multiple different pathways or multiple compounds may exert synergistic effects [33,37].…”

Section: Introductionmentioning

confidence: 99%

“…Metabolism disrupting chemicals (MDCs), their nuclear receptors (NRs) and other transcription factor targets, epigenetic modifications, and mitochondrial effects[27,[33][34][35][36][37][38][39]46,47].…”

mentioning

confidence: 99%

The EDCMET Project: Metabolic Effects of Endocrine Disruptors

Küblbeck

Vuorio

Niskanen

et al. 2020

IJMS

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Endocrine disruptors (EDs) are defined as chemicals that mimic, block, or interfere with hormones in the body’s endocrine systems and have been associated with a diverse array of health issues. The concept of endocrine disruption has recently been extended to metabolic alterations that may result in diseases, such as obesity, diabetes, and fatty liver disease, and constitute an increasing health concern worldwide. However, while epidemiological and experimental data on the close association of EDs and adverse metabolic effects are mounting, predictive methods and models to evaluate the detailed mechanisms and pathways behind these observed effects are lacking, thus restricting the regulatory risk assessment of EDs. The EDCMET (Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways) project brings together systems toxicologists; experimental biologists with a thorough understanding of the molecular mechanisms of metabolic disease and comprehensive in vitro and in vivo methodological skills; and, ultimately, epidemiologists linking environmental exposure to adverse metabolic outcomes. During its 5-year journey, EDCMET aims to identify novel ED mechanisms of action, to generate (pre)validated test methods to assess the metabolic effects of Eds, and to predict emergent adverse biological phenotypes by following the adverse outcome pathway (AOP) paradigm.

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Profiling of bisphenol A and eight of its analogues on transcriptional activity via human nuclear receptors

Cited by 108 publications

References 60 publications

Chemical components of plastics as endocrine disruptors: Overview and commentary

Chemical components of plastics as endocrine disruptors: Overview and commentary

In uteroestrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness

The EDCMET Project: Metabolic Effects of Endocrine Disruptors

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