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The Role of Endocrine-Disrupting Chemicals in the Human Health
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The Role of Endocrine-Disrupting Chemicals in the Human Health

A special issue of Journal of Xenobiotics (ISSN 2039-4713). This special issue belongs to the section "Emerging Chemicals".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 21354

Special Issue Editor

Dr. Elisa Cairrao

E-Mail Website
Guest Editor
1. CICS-UBI, Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal
2 FCS—UBI, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal
Interests: endocrine disruptors; human exposome; pregnancy exposome; phthalates; flame retardants; UVB-filters; bisphenols; cardiovascular endocrinology; fetoplacental vasculature; vascular smooth muscle cells; neurovascular unit; hypertensive disorders in pregnancy; hypothyroidism; calcium and potassium channels; sex hormones; patch clamp
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human exposure to various environmental contaminants called endocrine-disrupting chemicals (EDCs) is continuous and can lead to adverse effects on human health. Exposure to these EDCs is a global concern due to their adverse effects on the human endocrine system. Moreover, the cellular and molecular mechanisms by which EDCs interact with hormonal action are complex and difficult to understand. For this reason, knowledge of these mechanisms is one of the current challenges of endocrine research.

This Special Issue will focus on the advances of emerging contaminants’ role on human health. The aim is to provide an integrative, novel, and transdisciplinary approach to evaluate actual human exposure to EDC and contribute to the prevention and treatment of diseases. The theme is multidisciplinary, so I invite you to submit original research and review articles on the following non-exhaustive list of topics:

  • Environmental health;
  • Risk assessment;
  • Health impact assessment;
  • Endocrine-disrupting chemicals;
  • Cellular and molecular mechanistic;
  • In vitro studies;
  • Translational research;
  • Molecular docking.

Dr. Elisa Cairrao
Guest Editor

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. Journal of Xenobiotics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). 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 disruption
  • risk assessment
  • human exposome
  • emerging compounds
  • adverse outcomes pathways
  • animal translational studies

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Published Papers (9 papers)

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Research

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20 pages, 4798 KiB  
Article
Impact of Ex Vivo Bisphenol A Exposure on Gut Microbiota Dysbiosis and Its Association with Childhood Obesity
by Gracia Luque, Pilar Ortiz, Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Ana López-Moreno and Margarita Aguilera
J. Xenobiot. 2025, 15(1), 14; https://doi.org/10.3390/jox15010014 - 17 Jan 2025
Viewed by 627
Abstract
Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on [...] Read more.
Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum Bacteroidota, while taxa from the phylum Actinomycetota were promoted. Consistently, Bacteroides species were classified as sensitive to BPA, whereas bacteria belonging to the class Clostridia were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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15 pages, 2670 KiB  
Article
Prenatal Exposure to Bisphenol A and/or Diethylhexyl Phthalate Impacts Brain Monoamine Levels in Rat Offspring
by Amrita Kaimal, Jessica M. Hooversmith, Maryam H. Al Mansi, Philip V. Holmes, Puliyur S. MohanKumar and Sheba M. J. MohanKumar
J. Xenobiot. 2024, 14(3), 1036-1050; https://doi.org/10.3390/jox14030058 - 1 Aug 2024
Cited by 1 | Viewed by 1199
Abstract
This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered [...] Read more.
This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered saline, low doses (5 µg/kg BW/day) of BPA or DEHP, and their combination or a high dose (7.5 mg/kg BW/day) of DEHP alone or in combination with BPA during pregnancy. The offspring were subjected to a behavioral test and sacrificed in adulthood, and the brains were analyzed for neurotransmitter levels. In the paraventricular nucleus, there was a marked reduction in dopamine levels (p < 0.01) in male offspring from the BPA, DEHP, and B + D (HD) groups, which correlated well with their shock probe defensive burying times. Neurotransmitter changes in all brain regions examined were significant in female offspring, with DEHP (HD) females being affected the most, followed by the B + D groups. BPA and/or DEHP (LD) increased monoamine turnover in a region-specific manner in male offspring (p < 0.05). Overall, prenatal exposure to BPA, DEHP, or their combination alters monoamine levels in a brain region-specific, sex-specific, and dose-dependent manner, which could have implications for their behavioral and neuroendocrine effects. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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19 pages, 3399 KiB  
Article
Exposure to DEP Modifies the Human Umbilical Artery Vascular Resistance Contributing to Hypertension in Pregnancy
by Melissa Mariana, Amadeu M. V. M. Soares, Miguel Castelo-Branco and Elisa Cairrao
J. Xenobiot. 2024, 14(2), 497-515; https://doi.org/10.3390/jox14020030 - 18 Apr 2024
Viewed by 1576
Abstract
Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness [...] Read more.
Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness and endocrine disrupting properties, have been implicated in HDP in some epidemiological studies. Nevertheless, phthalates’ vascular impacts still need to be clarified. Thus, we aimed to understand the connection between phthalates exposure and the occurrence of gestational hypertension, as well as the pathway involved in the pathological vascular effects. We investigated diethyl phthalate’s (DEP) effect on the vascular reactivity of the human umbilical arteries (HUAs) from normotensive and hypertensive pregnant women. Both DEP’s nongenomic (within minutes effect) and genomic (24 h exposure to DEP) actions were evaluated, as well as the contribution of cyclic guanosine monophosphate and Ca2+ channel pathways. The results show that short-term exposure to DEP interferes with serotonin and histamine receptors, while after prolonged exposure, DEP seems to share the same vasorelaxant mechanism as estrogens, through the NO/sGC/cGMP/PKG signaling pathway, and to interfere with the L-type Ca2+ channels. Thus, the vascular effect induced by DEP is similar to that observed in HUA from hypertensive pregnancies, demonstrating that the development of HDP may be a consequence of DEP exposure. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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10 pages, 1056 KiB  
Article
Early Female Transgender Identity after Prenatal Exposure to Diethylstilbestrol: Report from a French National Diethylstilbestrol (DES) Cohort
by Laura Gaspari, Marie-Odile Soyer-Gobillard, Scott Kerlin, Françoise Paris and Charles Sultan
J. Xenobiot. 2024, 14(1), 166-175; https://doi.org/10.3390/jox14010010 - 12 Jan 2024
Cited by 1 | Viewed by 9998
Abstract
Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies [...] Read more.
Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies and lives as a woman. In recent decades, a significant increase in the number of transgender people has been reported. Although, its etiology is unknown, biological, anatomical, genetic, environmental and cultural factors have been suggested to contribute to gender variation. In XY animals, it has been shown that environmental endocrine disruptors, through their anti-androgenic activity, induce a female identity. In this work, we described four XY individuals who were exposed in utero to the xenoestrogen diethylstilbesterol (DES) and were part of the French HHORAGES cohort. They all reported a female transgender identity starting from childhood and adolescence. This high prevalence of male to female transgenderism (1.58%) in our cohort of 253 DES sons suggests that exposure to chemicals with xenoestrogen activity during fetal life may affect the male sex identity and behavior. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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Review

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31 pages, 2842 KiB  
Review
Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu
by Erica Buoso, Mirco Masi, Roberta Valeria Limosani, Chiara Oliviero, Sabrina Saeed, Martina Iulini, Francesca Carlotta Passoni, Marco Racchi and Emanuela Corsini
J. Xenobiot. 2025, 15(1), 13; https://doi.org/10.3390/jox15010013 - 17 Jan 2025
Viewed by 659
Abstract
Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term [...] Read more.
Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation. This is the case of bisphenol A (BPA), a well-known EDC whose tolerable daily intake (TDI) was re-evaluated in 2023 by the European Food Safety Authority (EFSA), and the immune system has been identified as the most sensitive to BPA exposure. Increasing scientific evidence indicates that EDCs can interfere with several hormone receptors, pathways and interacting proteins, resulting in a complex, cell context-dependent response that may differ among tissues. In this regard, the neuronal and immune systems are important targets of hormonal signaling and are now emerging as critical players in endocrine disruption. Here, we use BPA and its analogs as proof-of-concept EDCs to address their detrimental effects on the immune and nervous systems and to highlight complex interrelationships within the immune–neuroendocrine network (INEN). Finally, we propose that Receptor for Activated C Kinase 1 (RACK1), an important target for EDCs and a valuable screening tool, could serve as a central hub in our toxicology model to explain bisphenol-mediated adverse effects on the INEN. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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30 pages, 7117 KiB  
Review
Epigenetic Mechanisms of Endocrine-Disrupting Chemicals in Breast Cancer and Their Impact on Dietary Intake
by Desh Deepak Singh
J. Xenobiot. 2025, 15(1), 1; https://doi.org/10.3390/jox15010001 - 24 Dec 2024
Viewed by 1252
Abstract
Addressing the consequences of exposure to endocrine-disrupting chemicals (EDCs) demands thorough research and elucidation of the mechanism by which EDCs negatively impact women and lead to breast cancer (BC). Endocrine disruptors can affect major pathways through various means, including histone modifications, the erroneous [...] Read more.
Addressing the consequences of exposure to endocrine-disrupting chemicals (EDCs) demands thorough research and elucidation of the mechanism by which EDCs negatively impact women and lead to breast cancer (BC). Endocrine disruptors can affect major pathways through various means, including histone modifications, the erroneous expression of microRNA (miRNA), DNA methylation, and epigenetic modifications. However, it is still uncertain if the epigenetic modifications triggered by EDCs can help predict negative outcomes. Consequently, it is important to understand how different endocrine disrupters or signals interact with epigenetic modifications and regulate signalling mechanisms. This study proposes that the epigenome may be negatively impacted by several EDCs, such as cadmium, arsenic, lead, bisphenol A, phthalates, polychlorinated biphenyls and parabens, organochlorine, and dioxins. Further, this study also examines the impact of EDCs on lifestyle variables. In breast cancer research, it is essential to consider the potential impacts of EDC exposure and comprehend how EDCs function in tissues. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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40 pages, 8196 KiB  
Review
Impact of Endocrine Disruptors on the Genitourinary Tract
by Christophe Caneparo, Laurence Carignan, Elena Lonina, Sarah-Maude Goulet, Felix-Antoine Pellerin, Stéphane Chabaud, François Bordeleau, Stéphane Bolduc and Martin Pelletier
J. Xenobiot. 2024, 14(4), 1849-1888; https://doi.org/10.3390/jox14040099 - 2 Dec 2024
Viewed by 1460
Abstract
Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, [...] Read more.
Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, to an increasing presence of endocrine disruptors. These can be physical agents, such as light or heat; natural products, such as phytoestrogens; or chemicals produced by humans. Endocrine disruptors may interfere with the signaling pathways mediated by the endocrine system, particularly those linked to sex hormones. These factors and their general effects are presented before focusing on the male and female genitourinary tracts by describing their anatomy, development, and pathologies, including bladder and prostate cancer. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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28 pages, 1395 KiB  
Review
Polyphenols Regulate the Activity of Endocrine-Disrupting Chemicals, Having Both Positive and Negative Effects
by Eleonora Leti Maggio, Carlotta Zucca, Martina Grande, Raffaele Carrano, Antonio Infante, Riccardo Bei, Valeria Lucarini, Fernando De Maio, Chiara Focaccetti, Camilla Palumbo, Stefano Marini, Elisabetta Ferretti, Loredana Cifaldi, Laura Masuelli, Monica Benvenuto and Roberto Bei
J. Xenobiot. 2024, 14(4), 1378-1405; https://doi.org/10.3390/jox14040077 - 2 Oct 2024
Cited by 2 | Viewed by 1592
Abstract
Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with any hormone action. They are categorized according to origin and use, such as industrial chemicals like polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), plastics like bisphenol A (BPA), plasticizers like phthalates, pesticides like [...] Read more.
Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with any hormone action. They are categorized according to origin and use, such as industrial chemicals like polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), plastics like bisphenol A (BPA), plasticizers like phthalates, pesticides like dichlorodiphenyltrichloroethane (DDT), fungicides like vinclozolin, and pharmaceuticals like diethylstilbestrol (DES). Natural EDCs, such as phytoestrogens, are present in the diet of both humans and animals. Polyphenols are a large group of natural compounds derived from plants and are found in beverages and food. They are grouped based on their chemical structure into flavonoids and nonflavonoids and are reported to have many beneficial effects on health, including, but not limited to, anticancer, antioxidant, and anti-inflammatory effects. Moreover, polyphenols have both pro- and antioxidant characteristics, and due to their antioxidant and anti-inflammatory potential, they presumably have a protective effect against damage induced by EDCs. However, polyphenols may act as EDCs. In this review, we report that polyphenols regulate the activity of EDCs, having both positive and negative effects. Hence, a better understanding of the associations between EDCs and polyphenols will allow the establishment of improved approaches to protect human health from EDCs. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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28 pages, 3684 KiB  
Review
How Per- and Poly-Fluoroalkyl Substances Affect Gamete Viability and Fertilization Capability: Insights from the Literature
by Cielle Lockington and Laura A. Favetta
J. Xenobiot. 2024, 14(2), 651-678; https://doi.org/10.3390/jox14020038 - 17 May 2024
Cited by 1 | Viewed by 1806
Abstract
There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3–8.5 years). In females, PFAS inhibit the [...] Read more.
There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3–8.5 years). In females, PFAS inhibit the hypothalamic–pituitary–gonadal (HPG) axis, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to the inhibition of androgen and estradiol production. PFAS have been found to cause detrimental effects on egg quality through impairing folliculogenesis. In males, PFAS can impair sperm motility and morphology: two fundamental qualities of successful fertilization. PFAS exposure has been proven to inhibit testosterone production, sperm capacitation, and acrosomal reaction. After fertilization, the results of PFAS exposure to embryos have also been investigated, showing reduced development to the blastocyst stage. The aim of this review is to report the main findings in the literature on the impact of PFAS exposure to gamete competency and fertilization capability by highlighting key studies on both male and female fertility. We report that there is significant evidence demonstrating the negative impacts on fertility after PFAS exposure. At high doses, these environmentally abundant and widespread compounds can significantly affect human fertility. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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