scholarly journals Perturbation of Nuclear Hormone Receptors by Endocrine Disrupting Chemicals: Mechanisms and Pathological Consequences of Exposure

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 13 ◽  
Author(s):  
Julie M. Hall ◽  
Callie W. Greco
Keyword(s):  
Hormone Receptors ◽  
Endocrine Disrupting Chemicals ◽  
Type Ii Diabetes Mellitus ◽  
Epidemiological Studies ◽  
Nuclear Hormone Receptors ◽  
Sex Steroid Hormone ◽  
Organ Systems ◽  
Endocrine Disrupting ◽  
The Central Nervous System ◽  
And Function

Much of the early work on Nuclear Hormone Receptors (NHRs) focused on their essential roles as mediators of sex steroid hormone signaling in reproductive development and function, and thyroid hormone-dependent formation of the central nervous system. However, as NHRs display tissue-specific distributions and activities, it is not surprising that they are involved and vital in numerous aspects of human development and essential for homeostasis of all organ systems. Much attention has recently been focused on the role of NHRs in energy balance, metabolism, and lipid homeostasis. Dysregulation of NHR function has been implicated in numerous pathologies including cancers, metabolic obesity and syndrome, Type II diabetes mellitus, cardiovascular disease, hyperlipidemia, male and female infertility and other reproductive disorders. This review will discuss the dysregulation of NHR function by environmental endocrine disrupting chemicals (EDCs), and the associated pathological consequences of exposure in numerous tissues and organ systems, as revealed by experimental, clinical, and epidemiological studies.

scholarly journals G-Protein Coupled Hormone Receptors of the Hypothalamic-Pituitary-Gonadal Axis are Targets of Endocrine Disrupting Chemicals

2021 ◽  
Author(s):  
Valentine Suteau ◽  
Patrice Rodien ◽  
Mathilde Munier
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Follicle Stimulating Hormone ◽  
Endocrine Disrupting Chemicals ◽  
Reproductive Function ◽  
Epidemiological Studies ◽  
Gonadotropin Releasing Hormone ◽  
Membrane Receptors ◽  
Endocrine Disrupting ◽  
G Protein Coupled

Endocrine-disrupting chemicals have received significant concern, since they ubiquitously persist in the environment and are able to induce adverse effects on health, and more particularly on reproductive function. Most of the studies focused on nuclear hormone receptors as mediators of sex steroid hormones signaling. However, there are increasing evidences that peptides hormones of the Hypothalamo-Pituitary-Gonadal axis are targets of endocrine-disrupting chemicals (as Gonadotropin-Releasing Hormone, Follicle-Stimulating Hormone, Luteinizing Hormone…). The majority of these hormones act on G protein-coupled membrane receptors. This review summarizes the effects of endocrine-disrupting chemicals on homeostasis of peptides hormone of Hypothalamo-Pituitary-Gonadal axis and on their G protein-coupled membrane receptors signaling revealed by experimental, clinical, and epidemiological studies in human.

scholarly journals Endocrine-Disrupting Chemicals and Insulin Resistance in Children

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 137 ◽  
Author(s):  
Eleonora Rotondo ◽  
Francesco Chiarelli
Keyword(s):  
Insulin Resistance ◽  
Bisphenol A ◽  
Prospective Studies ◽  
Endocrine Disrupting Chemicals ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Cross Sectional ◽  
Obesity And Diabetes ◽  
Endocrine Disrupting ◽  
Background Exposure

The purpose of this article is to review the evidence linking background exposure to endocrine-disrupting chemicals (EDCs) with insulin resistance in children. Although evidence in children is scarce since very few prospective studies exist even in adults, evidence that EDCs might be involved in the development of insulin resistance and related diseases such as obesity and diabetes is accumulating. We reviewed the literature on both cross-sectional and prospective studies in humans and experimental studies. Epidemiological studies show a statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, aromatic polycyclic hydrocarbides, or dioxins and insulin resistance.

scholarly journals Effects of endocrine disruptors in the development of the female reproductive tract

2014 ◽  
Vol 58 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Elaine Maria Frade Costa ◽  
Poli Mara Spritzer ◽  
Alexandre Hohl ◽  
Tânia A. S. S. Bachega
Keyword(s):  
Endocrine Disruptors ◽  
Hormone Receptors ◽  
Reproductive Tract ◽  
Polycystic Ovary ◽  
Endocrine Disrupting Chemicals ◽  
Public Health Problem ◽  
Female Reproductive Tract ◽  
Major Public Health Problem ◽  
Endocrine Disrupting ◽  
Environmental Agencies

Environmental agencies have identified a growing number of environmental contaminants that have endocrine disrupting activity, and these can become a major public health problem. It is suggested that endocrine disruptors could account for the higher-than-expected increase in the prevalence of some non-communicable diseases, such as obesity, diabetes, thyroid diseases, and some cancers. Several endocrine Disrupting Chemicals (EDCs), such as pesticides, bisphenol A, phthalates, dioxins, and phytoestrogens, can interact with the female reproductive system and lead to endocrine disruption. Initially, it was assumed that EDCs exert their effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the synthesis or catabolism of steroids. Biomonitoring studies have identified these compounds in adults, children, pregnant women, and fetuses. Among the diseases of the female reproductive tract associated with EDCs exposure are the following: precocious puberty, polycystic ovary syndrome, and premature ovarian failure. The different populations of the world are exposed to a great number of chemicals through different routes of infection; despite the various available studies, there is still much doubt regarding the additive effect of a mixture of EDCs with similar mechanisms of action.

3D-QSAR study of the endocrine disrupting effect of perfluorooctane sulfonates (PFOS) and perfluorooctanoic acid (PFOA) on human estrogen, androgen and thyroid receptors

2010 ◽  
Vol 75 (4) ◽  
pp. 471-492 ◽  
Author(s):  
Yan Cheng ◽  
Hui-ming Chen ◽  
Wen-lian Yu ◽  
Yuan Cui ◽  
Li-li Zhou ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
3D Qsar ◽  
Perfluorooctanoic Acid ◽  
Epidemiological Studies ◽  
Binding Energies ◽  
Human Thyroid ◽  
Binding Modes ◽  
Mechanism Study ◽  
Qsar Study ◽  
Endocrine Disrupting

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have become emerging persistent organic pollutants (POPs), but their health effects on humans remain controversial because of contradictory experimental and epidemiological studies. In this study, we used three-dimensional quantitative structure–activity relationship (3D-QSAR) method by applying Surflex-dock to study and compare the binding modes between PFOS, PFOA and eight other endocrine disrupting chemicals, and human estrogen receptor (hERα), human androgen receptor (hAR) and human thyroid receptor (hTRβ). Molecular docking and hydrogen bond studies indicated that PFOS and PFOA had high affinity potency toward hERα, hAR and hTRβ due to low free binding energies, while the highest value was obtained toward hTRβ. This means that PFOS and PFOA might have more disrupting effects on thyroid than on estrogen and androgen receptors. Hydrogen bonding interactions revealed that Met313 in hTRβ might act as the critical amino acid residue in the binding of ligand–receptor complex, which would provide an explanation for the interaction mechanisms. Our results provide an important reference and direction for the interaction mode and mechanism study between PFOS/PFOA and human endocrine systems.

scholarly journals Assessment and Molecular Actions of Endocrine-Disrupting Chemicals That Interfere with Estrogen Receptor Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Gwenneg Kerdivel ◽  
Denis Habauzit ◽  
Farzad Pakdel
Keyword(s):  
Synergistic Effects ◽  
Animal Health ◽  
Endocrine Disrupting Chemicals ◽  
Estrogen Signaling ◽  
Synthetic Chemicals ◽  
Endocrine Disrupting ◽  
And Function ◽  
Analytical Tools

In all vertebrate species, estrogens play a crucial role in the development, growth, and function of reproductive and nonreproductive tissues. A large number of natural or synthetic chemicals present in the environment and diet can interfere with estrogen signaling; these chemicals are called endocrine disrupting chemicals (EDCs) or xenoestrogens. Some of these compounds have been shown to induce adverse effects on human and animal health, and some compounds are suspected to contribute to diverse disease development. Because xenoestrogens have varying sources and structures and could act in additive or synergistic effects when combined, they have multiple mechanisms of action. Consequently, an important panel ofin vivoandin vitrobioassays and chemical analytical tools was used to screen, evaluate, and characterize the potential impacts of these compounds on humans and animals. In this paper, we discuss different molecular actions of some of the major xenoestrogens found in food or the environment, and we summarize the current models used to evaluate environmental estrogens.

scholarly journals Transcriptomics and Other Omics Approaches to Investigate Effects of Xenobiotics on the Placenta

2021 ◽  
Vol 9 ◽  
Author(s):  
Cheryl S. Rosenfeld
Keyword(s):  
Expression Patterns ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine System ◽  
Environmental Toxicants ◽  
Bisphenol S ◽  
Extrinsic Factors ◽  
Placental Function ◽  
Organ Systems ◽  
Endocrine Disrupting ◽  
Pharmaceutical Agents

The conceptus is most vulnerable to developmental perturbation during its early stages when the events that create functional organ systems are being launched. As the placenta is in direct contact with maternal tissues, it readily encounters any xenobiotics in her bloodstream. Besides serving as a conduit for solutes and waste, the placenta possesses a tightly regulated endocrine system that is, of itself, vulnerable to pharmaceutical agents, endocrine disrupting chemicals (EDCs), and other environmental toxicants. To determine whether extrinsic factors affect placental function, transcriptomics and other omics approaches have become more widely used. In casting a wide net with such approaches, they have provided mechanistic insights into placental physiological and pathological responses and how placental responses may impact the fetus, especially the developing brain through the placenta-brain axis. This review will discuss how such omics technologies have been utilized to understand effects of EDCs, including the widely prevalent plasticizers bisphenol A (BPA), bisphenol S (BPS), and phthalates, other environmental toxicants, pharmaceutical agents, maternal smoking, and air pollution on placental gene expression, DNA methylation, and metabolomic profiles. It is also increasingly becoming clear that miRNA (miR) are important epigenetic regulators of placental function. Thus, the evidence to date that xenobiotics affect placental miR expression patterns will also be explored. Such omics approaches with mouse and human placenta will assuredly provide key biomarkers that may be used as barometers of exposure and can be targeted by early mitigation approaches to prevent later diseases, in particular neurobehavioral disorders, originating due to placental dysfunction.

scholarly journals Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer

2020 ◽  
Vol 21 (23) ◽  
pp. 9139
Author(s):  
Louisane Eve ◽  
Béatrice Fervers ◽  
Muriel Le Romancer ◽  
Nelly Etienne-Selloum
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Disease Incidence ◽  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Environmental Chemicals ◽  
Endocrine Disrupting ◽  
Carcinogenic Effects ◽  
The Many

Breast cancer (BC) is the second most common cancer and the fifth deadliest in the world. Exposure to endocrine disrupting pollutants has been suggested to contribute to the increase in disease incidence. Indeed, a growing number of researchershave investigated the effects of widely used environmental chemicals with endocrine disrupting properties on BC development in experimental (in vitro and animal models) and epidemiological studies. The complex effects of endocrine disrupting chemicals (EDCs) on hormonal pathways, involving carcinogenic effects and an increase in mammary gland susceptibility to carcinogenesis—together with the specific characteristics of the mammary gland evolving over the course of life and the multifactorial etiology of BC—make the evaluation of these compounds a complex issue. Among the many EDCs suspected of increasing the risk of BC, strong evidence has only been provided for few EDCs including diethylstilbestrol, dichlorodiphenyltrichloroethane, dioxins and bisphenol A. However, given the ubiquitous nature and massive use of EDCs, it is essential to continue to assess their long-term health effects, particularly on carcinogenesis, to eradicate the worst of them and to sensitize the population to minimize their use.

scholarly journals Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis

2020 ◽  
Vol 11 ◽  
Author(s):  
Margarita Aguilera ◽  
Yolanda Gálvez-Ontiveros ◽  
Ana Rivas
Keyword(s):  
Gut Microbiota ◽  
Steroid Hormones ◽  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Host Susceptibility ◽  
Research Strategies ◽  
Microbial Composition ◽  
Endocrine Disrupting ◽  
The Impact

Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term “endobolome” when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed “microbiota disrupting chemicals” (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.

In utero exposure to persistent and nonpersistent endocrine-disrupting chemicals and anogenital distance. A systematic review of epidemiological studies†

2019 ◽  
Vol 102 (2) ◽  
pp. 276-291 ◽  
Author(s):  
William Nelson ◽  
Ding-Yuan Liu ◽  
Yin Yang ◽  
Zhao-Hui Zhong ◽  
Ying-Xiong Wang ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Female Offspring ◽  
Epidemiological Studies ◽  
In Utero ◽  
In Utero Exposure ◽  
Inverse Association ◽  
Anthropometric Parameter ◽  
Cumulative Impact ◽  
Anogenital Distance ◽  
Endocrine Disrupting

Abstract Anti-androgenic endocrine-disrupting chemicals (EDCs) can cross the placenta to modify early offspring sexual dimorphic markers. These changes are linked to anogenital distance (AGD), which is an androgen-sensitive anthropometric parameter used as a biomarker of perineal growth and caudal migration of the genital tubercle. This review aimed to summarize strength of evidence for associations of in utero exposure to EDCs with AGD and to identify gaps and limitations in the literature so as to inform future research. We performed an electronic search of English literature in September 2019 in medical literature analysis and retrieval system online (MEDLINE), Web of Science and Toxline. We included epidemiological studies that examined in utero exposure to persistent and nonpersistent EDCs and considered AGD in offspring as an outcome. Our review contained 16 investigations examining exposure to persistent EDCs (nine studies) and nonpersistent EDCs (seven studies). Some individual studies reported an inverse association between exposure to bisphenol A (BPA), dioxins, perfluoroalkyl substances, and organochlorides and AGD in both male and female offspring. Meta-analysis of three studies found a small reduction of AGD in female offspring exposed to BPA. The number of studies per chemical is small, and number of subjects examined is limited; so, replication of these results is needed. To achieve more specificity and better replication of results, future studies should establish the association of nonpersistent EDCs using multiple urine samples, evaluate the cumulative impact of exposure to a mixture of anti-androgenic chemicals, and offer adequate consideration of more maternal- and children-related confounding factors.

Exposure to Endocrine Disrupting Chemicals and Children's Health: Problems in Epidemiological Studies

2006 ◽  
Vol 61 (1) ◽  
pp. 19-31 ◽  
Author(s):  
Reiko KISHI ◽  
Fumihiro SATA ◽  
Yasuaki SAIJO ◽  
Norie KURAHASHI ◽  
Shizue KATO ◽  
...  
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Health Problems ◽  
Children's Health ◽  
Children’S Health ◽  
Endocrine Disrupting
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