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      Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

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          Abstract

          Endocrine disrupting chemicals (EDCs) play a part in the modern burst of diseases and interfere with the steroid hormone axis. Bisphenol A (BPA), one of the most active and widely used EDCs, affects ameloblast functions, leading to an enamel hypomineralization pattern similar to that of Molar Incisor Hypomineralization (MIH). In order to explore the molecular pathways stimulated by BPA during amelogenesis, we thoroughly investigated the receptors known to directly or indirectly mediate the effects of BPA. The expression patterns of high affinity BPA receptors (ERRγ, GPR30), of ketosteroid receptors (ERs, AR, PGR, GR, MR), of the retinoid receptor RXRα, and PPARγ were established using RT-qPCR analysis of RNAs extracted from microdissected enamel organ of adult rats. Their expression was dependent on the stage of ameloblast differentiation, except that of ERβ and PPARγ which remained undetectable. An additional large scale microarray analysis revealed three main groups of receptors according to their level of expression in maturation-stage ameloblasts. The expression level of RXRα was the highest, similar to the vitamin D receptor (VDR), whereas the others were 13 to 612-fold lower, with AR and GR being intermediate. Immunofluorescent analysis of VDR, ERα and AR confirmed their presence mainly in maturation- stage ameloblasts. These data provide further evidence that ameloblasts express a specific combination of hormonal receptors depending on their developmental stage. This study represents the first step toward understanding dental endocrinology as well as some of the effects of EDCs on the pathophysiology of amelogenesis.

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          Most cited references32

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          Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes.

          Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) α and β differ from that used by 17β-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17β-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor γ and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.
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            Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

            Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases.
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              Evidence for bisphenol A-induced female infertility: a review (2007-2016).

              We summarized the scientific literature published from 2007 to 2016 on the potential effects of bisphenol A (BPA) on female fertility. We focused on overall fertility outcomes (e.g., ability to become pregnant, number of offspring), organs that are important for female reproduction (i.e., oviduct, uterus, ovary, hypothalamus, and pituitary), and reproductive-related processes (i.e., estrous cyclicity, implantation, and hormonal secretion). The reviewed literature indicates that BPA may be associated with infertility in women. Potential explanations for this association can be generated from experimental studies. Specifically, BPA may alter overall female reproductive capacity by affecting the morphology and function of the oviduct, uterus, ovary, and hypothalamus-pituitary-ovarian axis in animal models. In addition, BPA may disrupt estrous cyclicity and implantation. Nevertheless, further studies are needed to better understand the exact mechanisms of action and to detect potential reproductive toxicity at earlier stages.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                02 November 2016
                2016
                : 7
                : 503
                Affiliations
                [1] 1Paris Laboratory of Molecular Oral Pathophysiology, Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale UMRS 1138, Université Paris-Descartes, Université Pierre et Marie Curie-Paris Paris, France
                [2] 2Université Paris-Diderot, Unité de Formation et de Recherche d'Odontologie Paris, France
                [3] 3Centre de Référence des maladies rares de la face et de la cavité buccale MAFACE hôpital Rothschild, AP-HP Paris, France
                Author notes

                Edited by: Thimios Mitsiadis, University of Zurich, Switzerland

                Reviewed by: Javier Catón, CEU San Pablo University, Spain; Victor E. Arana-Chavez, University of São Paulo, Brazil; Supawadee Sukseree, Medical University of Vienna, Austria

                *Correspondence: Sylvie Babajko sylvie.babajko@ 123456crc.jussieu.fr

                This article was submitted to Craniofacial Biology and Dental Research, a section of the journal Frontiers in Physiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fphys.2016.00503
                5090168
                27853434
                0ebb2190-ab2c-422e-b5ac-6d939e4d9b33
                Copyright © 2016 Houari, Loiodice, Jedeon, Berdal and Babajko.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 August 2016
                : 13 October 2016
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 45, Pages: 9, Words: 5835
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                amelogenesis,steroid receptors,steroid hormones,endocrine disrupting chemicals,enamel mineralization

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