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Advances in Endocrine Disruptors 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 34010

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Special Issue Editors

Prof. Dr. Nicolas Chevalier

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Guest Editor

Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, Service d'Endocrinologie, Diabétologie et Médecine de la Reproduction, Inserm U1065, 06000 Nice, France
Interests: endocrine disruptors; epidemiology; cancer; reproductive tract; endocrine disorders; thyroid; obesity
Special Issues, Collections and Topics in MDPI journals

Dr. Charlotte Hinault-Boyer

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Guest Editor

Centre Hospitalier Universitaire de Nice, Hôpital Pasteur, Laboratoire de Biochimie-Hormonologie, Inserm U1065, 06000 Nice, France
Interests: endocrine disruptors; adipose tissue; cancer; obesity; fetal programming; mass spectrometry; biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endocrine disruption is now considered a major health concern affecting all people worldwide. For the last few years, a large number of clinical and experimental studies have deepened and progressed our knowledge of the molecular mechanisms involved in endocrine disruption. Nevertheless, some issues still need to be documented: non-monotonic effects (low-dose effects), non-classical steroid receptors, new signaling pathways, the adverse effects of mixtures, transgenerational effects, and new screening tools. Furthermore, some data suggest that endocrine disruption is also observed with non-chemical factors (millimeter wave radiation, lightning cycles, and chronic stress following the recent lockdown, etc.) and affects new endocrine systems, such as the parathyroid glands, adrenals, neurocognitive regulation, and taste regulation.

This Special Issue is a continuation of the successful issue “Advances in Endocrine Disruptors”, which aims to review current advances in the field of endocrine disruption with the purpose of better understanding these unmet needs. Contributions to both animal models and/or humans, as well as to alternative tools, are encouraged, to shed light on the development of new hypotheses about endocrine disruption.

Prof. Dr. Nicolas Chevalier
Dr. Charlotte Hinault-Boyer
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

endocrine disruptor
non-monotonic effects
low-dose effects
mixtures
chemical agents
physical agents
non-classical receptors
cancer
reproductive tract
thyroid
adrenal
parathyroid glands
neurocognitive effects
obesity
diabetes
metabolic disorders
transgenerational effects
epigenetics
biomarkers
screening tools

Published Papers (10 papers)

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Research

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15 pages, 4218 KiB

Open AccessArticle

A Mixture of Chemicals Found in Human Amniotic Fluid Disrupts Brain Gene Expression and Behavior in Xenopus laevis

by Michelle Leemans, Petra Spirhanzlova, Stephan Couderq, Sébastien Le Mével, Alexis Grimaldi, Evelyne Duvernois-Berthet, Barbara Demeneix and Jean-Baptiste Fini

Int. J. Mol. Sci. 2023, 24(3), 2588; https://doi.org/10.3390/ijms24032588 - 30 Jan 2023

Cited by 1 | Viewed by 1808

Abstract

Thyroid hormones (TH) are essential for normal brain development, influencing neural cell differentiation, migration, and synaptogenesis. Multiple endocrine-disrupting chemicals (EDCs) are found in the environment, raising concern for their potential effects on TH signaling and the consequences on neurodevelopment and behavior. While most research on EDCs investigates the effects of individual chemicals, human health may be adversely affected by a mixture of chemicals. The potential consequences of EDC exposure on human health are far-reaching and include problems with immune function, reproductive health, and neurological development. We hypothesized that embryonic exposure to a mixture of chemicals (containing phenols, phthalates, pesticides, heavy metals, and perfluorinated, polychlorinated, and polybrominated compounds) identified as commonly found in the human amniotic fluid could lead to altered brain development. We assessed its effect on TH signaling and neurodevelopment in an amphibian model (Xenopus laevis) highly sensitive to thyroid disruption. Fertilized eggs were exposed for eight days to either TH (thyroxine, T₄ 10 nM) or the amniotic mixture (at the actual concentration) until reaching stage NF47, where we analyzed gene expression in the brains of exposed tadpoles using both RT-qPCR and RNA sequencing. The results indicate that whilst some overlap on TH-dependent genes exists, T₄ and the mixture have different gene signatures. Immunohistochemistry showed increased proliferation in the brains of T₄-treated animals, whereas no difference was observed for the amniotic mixture. Further, we demonstrated diminished tadpoles’ motility in response to T₄ and mixture exposure. As the individual chemicals composing the mixture are considered safe, these results highlight the importance of examining the effects of mixtures to improve risk assessment. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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13 pages, 16504 KiB

Open AccessArticle

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

by Ramona D’Amico, Davide Di Paola, Daniela Impellizzeri, Tiziana Genovese, Roberta Fusco, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Livia Interdonato, Salvatore Cuzzocrea, Rosanna Di Paola, Rosalba Siracusa and Marika Cordaro

Int. J. Mol. Sci. 2022, 23(19), 11320; https://doi.org/10.3390/ijms231911320 - 26 Sep 2022

Cited by 4 | Viewed by 1506

Abstract

Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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14 pages, 8626 KiB

Open AccessArticle

Low Doses of PFOA Promote Prostate and Breast Cancer Cells Growth through Different Pathways

by Aurélie Charazac, Charlotte Hinault, Bastien Dolfi, Solène Hautier, Célia Decondé Le Butor, Frédéric Bost and Nicolas Chevalier

Int. J. Mol. Sci. 2022, 23(14), 7900; https://doi.org/10.3390/ijms23147900 - 18 Jul 2022

Cited by 5 | Viewed by 2485

Abstract

Endocrine Disrupting Compounds (EDCs) are found in everyday products. Widely distributed throughout the environment, persistent organic pollutants (POPs) are a specific class of EDCs that can accumulate in adipose tissue. Many of them induce adverse effects on human health—such as obesity, fertility disorders and cancers—by perturbing hormone effects. We previously identified many compounds with EDC activity in the circulation of obese patients who underwent bariatric surgery. Herein, we analyzed the effects of four of them (aldrin, BDE28, PFOA and PCB153) on two cancer cell lines of hormone-sensitive organs (prostate and breast). Each cell line was exposed to serial dilutions of EDCs from 10⁻⁶ M to 10⁻¹² M; cytotoxicity and proliferation were monitored using the IncuCyte^® technology. We showed that none of these EDCs induce cytotoxicity and that PFOA and PCB153, only at very low doses (10⁻¹² M), increase the proliferation of DU145 (prostate cancer) and MCF7 (breast cancer) cells, while the same effects are observed with high concentrations (10⁻⁶ M) for aldrin or BDE28. Regarding the mechanistic aspects, PFOA uses two different signaling pathways between the two lines (the Akt/mTORC1 and PlexinD1 in MCF7 and DU145, respectively). Thus, our study demonstrates that even at picomolar (10⁻¹² M) concentrations PFOA and PCB153 increase the proliferation of prostate and breast cancer cell lines and can be considered possible carcinogens. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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Review

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24 pages, 4338 KiB

Open AccessReview

Is Physical Activity an Efficient Strategy to Control the Adverse Effects of Persistent Organic Pollutants in the Context of Obesity? A Narrative Review

by Quentin A. Serrano, Sébastien Le Garf, Vincent Martin, Serge S. Colson and Nicolas Chevalier

Int. J. Mol. Sci. 2024, 25(2), 883; https://doi.org/10.3390/ijms25020883 - 10 Jan 2024

Viewed by 831

Abstract

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs’ adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis, and gut microbiota dysbiosis, that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery, where weight loss promotes POPs’ blood release. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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18 pages, 1169 KiB

Open AccessReview

Endocrine-Disrupting Chemicals and Disease Endpoints

by Changhwan Ahn and Eui-Bae Jeung

Int. J. Mol. Sci. 2023, 24(6), 5342; https://doi.org/10.3390/ijms24065342 - 10 Mar 2023

Cited by 25 | Viewed by 6512

Abstract

Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems, and have been shown to interfere with physiological systems, especially by disrupting the hormone balance. During the last few decades, EDCs have been shown to affect reproductive, neurological, and metabolic development and function and even stimulate tumor growth. EDC exposure during development can disrupt normal development patterns and alter susceptibility to disease. Many chemicals have endocrine-disrupting properties, including bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols, and phthalates. These compounds have gradually been elucidated as risk factors for many diseases, such as reproductive, neural, and metabolic diseases and cancers. Endocrine disruption has been spread to wildlife and species that are connected to the food chains. Dietary uptake represents an important source of EDC exposure. Although EDCs represent a significant public health concern, the relationship and specific mechanism between EDCs and diseases remain unclear. This review focuses on the disease-EDC relationship and the disease endpoints associated with endocrine disruption for a better understanding of the relationship between EDCs-disease and elucidates the development of new prevention/treatment opportunities and screening methods. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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20 pages, 1299 KiB

Open AccessReview

Critical Overview on Endocrine Disruptors in Diabetes Mellitus

by Charlotte Hinault, Philippe Caroli-Bosc, Frédéric Bost and Nicolas Chevalier

Int. J. Mol. Sci. 2023, 24(5), 4537; https://doi.org/10.3390/ijms24054537 - 25 Feb 2023

Cited by 8 | Viewed by 3079

Abstract

Diabetes mellitus is a major public health problem in all countries due to its high human and economic burden. Major metabolic alterations are associated with the chronic hyperglycemia that characterizes diabetes and causes devastating complications, including retinopathy, kidney failure, coronary disease and increased cardiovascular mortality. The most common form is type 2 diabetes (T2D) accounting for 90 to 95% of the cases. These chronic metabolic disorders are heterogeneous to which genetic factors contribute, but so do prenatal and postnatal life environmental factors including a sedentary lifestyle, overweight, and obesity. However, these classical risk factors alone cannot explain the rapid evolution of the prevalence of T2D and the high prevalence of type 1 diabetes in particular areas. Among environmental factors, we are in fact exposed to a growing amount of chemical molecules produced by our industries or by our way of life. In this narrative review, we aim to give a critical overview of the role of these pollutants that can interfere with our endocrine system, the so-called endocrine-disrupting chemicals (EDCs), in the pathophysiology of diabetes and metabolic disorders. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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19 pages, 762 KiB

Open AccessReview

Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels

by Ana C. Marques, Melissa Mariana and Elisa Cairrao

Int. J. Mol. Sci. 2022, 23(19), 11427; https://doi.org/10.3390/ijms231911427 - 28 Sep 2022

Cited by 5 | Viewed by 2715

Abstract

Hygiene is essential to avoid diseases, and this is thanks to daily cleaning and disinfection habits. Currently, there are numerous commercial products containing antimicrobial agents, and although they are efficient in disinfecting, it is still not known the effect of the constant use of these products on human health. In fact, a massive use of disinfectants has been observed due to COVID-19, but the possible adverse effects are not yet known. Triclosan is one of the antimicrobial agents used in cosmetic products, toothpaste, and disinfectants. This compound is an endocrine disruptor, which means it can interfere with hormonal function, with its estrogenic and androgenic activity having already been stated. Even if the use of triclosan is well-regulated, with the maximum allowed concentration in the European Union of 0.3% (m/m), its effects on human health are still uncertain. Studies in animals and humans suggest the possibility of harmful health outcomes, particularly for the reproductive system, and in a less extent for the cardiovascular and thyroid functions. Thus, the purpose of this review was to analyse the possible implications of the massive use of triclosan, mainly on the reproductive and cardiovascular systems and on the thyroid function, both in animals and humans. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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23 pages, 606 KiB

Open AccessReview

Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens

by Mai Nguyen and Clodia Osipo

Int. J. Mol. Sci. 2022, 23(12), 6813; https://doi.org/10.3390/ijms23126813 - 18 Jun 2022

Cited by 12 | Viewed by 4105

Abstract

Breast cancer therapies have made significant strides in improving survival for patients over the past decades. However, recurrence and drug resistance continue to challenge long-term recurrence-free and overall survival rates. Mounting evidence supports the cancer stem cell model in which the existence of a small population of breast cancer stem cells (BCSCs) within the tumor enables these cells to evade conventional therapies and repopulate the tumor, giving rise to more aggressive, recurrent tumors. Thus, successful breast cancer therapy would need to target these BCSCs, as well the tumor bulk cells. Since the Women’s Health Initiative study reported an increased risk of breast cancer with the use of conventional hormone replacement therapy in postmenopausal women, many have turned their attention to phytoestrogens as a natural alternative. Phytoestrogens are plant compounds that share structural similarities with human estrogens and can bind to the estrogen receptors to alter the endocrine responses. Recent studies have found that phytoestrogens can also target BCSCs and have the potential to complement conventional therapy eradicating BCSCs. This review summarized the latest findings of different phytoestrogens and their effect on BCSCs, along with their mechanisms of action, including selective estrogen receptor binding and inhibition of molecular pathways used by BCSCs. The latest results of phytoestrogens in clinical trials are also discussed to further evaluate the use of phytoestrogen in the treatment and prevention of breast cancer. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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20 pages, 657 KiB

Open AccessReview

Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System

by Valentina Guarnotta, Roberta Amodei, Francesco Frasca, Antonio Aversa and Carla Giordano

Int. J. Mol. Sci. 2022, 23(10), 5710; https://doi.org/10.3390/ijms23105710 - 20 May 2022

Cited by 28 | Viewed by 6851

Abstract

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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15 pages, 1049 KiB

Open AccessReview

Are BPA Substitutes as Obesogenic as BPA?

by Fabiana Oliviero, Alice Marmugi, Catherine Viguié, Véronique Gayrard, Nicole Picard-Hagen and Laila Mselli-Lakhal

Int. J. Mol. Sci. 2022, 23(8), 4238; https://doi.org/10.3390/ijms23084238 - 11 Apr 2022

Cited by 23 | Viewed by 3326

Abstract

Metabolic diseases, such as obesity, Type II diabetes and hepatic steatosis, are a significant public health concern affecting more than half a billion people worldwide. The prevalence of these diseases is constantly increasing in developed countries, affecting all age groups. The pathogenesis of metabolic diseases is complex and multifactorial. Inducer factors can either be genetic or linked to a sedentary lifestyle and/or consumption of high-fat and sugar diets. In 2002, a new concept of “environmental obesogens” emerged, suggesting that environmental chemicals could play an active role in the etiology of obesity. Bisphenol A (BPA), a xenoestrogen widely used in the plastic food packaging industry has been shown to affect many physiological functions and has been linked to reproductive, endocrine and metabolic disorders and cancer. Therefore, the widespread use of BPA during the last 30 years could have contributed to the increased incidence of metabolic diseases. BPA was banned in baby bottles in Canada in 2008 and in all food-oriented packaging in France from 1 January 2015. Since the BPA ban, substitutes with a similar structure and properties have been used by industrials even though their toxic potential is unknown. Bisphenol S has mainly replaced BPA in consumer products as reflected by the almost ubiquitous human exposure to this contaminant. This review focuses on the metabolic effects and targets of BPA and recent data, which suggest comparable effects of the structural analogs used as substitutes. Full article

(This article belongs to the Special Issue Advances in Endocrine Disruptors 2.0)

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