Environmental Endocrine Disrupting Chemicals and Cardiac Arrhythmogenesis

Total Page:16

File Type:pdf, Size:1020Kb

Environmental Endocrine Disrupting Chemicals and Cardiac Arrhythmogenesis Environmental Endocrine Disrupting Chemicals and Cardiac Arrhythmogenesis A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in the Department of Pharmacology and Cell Biophysics of the College of Medicine By Xiaoqian Gao B.S. Sichuan University Huaxi Medical Center, 2009 Committee Chairperson: Hong-Sheng Wang, Ph.D. Abstract Environmental endocrine disrupting chemicals (EDCs) are a group of exogenous compounds that may interfere with the functioning of endogenous systems and affect human health. Bisphenol A (BPA) is one of most ubiquitous EDCs in the manufacturing industry as a plasticizing agent used in polycarbonate plastics and epoxy resins. It is well-documented that human exposure to BPA is extremely wide spread. It was demonstrated that BPA, at human-exposure relevant doses, rapidly promoted cardiac arrhythmias in female rat hearts. However, the molecular mechanisms underlying BPA’s pro-arrhythmic effects remain unclear. As a result of banning BPA’s use in various consumer products, bisphenol S (BPS) is increasingly used as a substitute agent for BPA. Human populations are reported to be widely exposed to BPS, but the biological activities and potential toxic effects of BPS are not well understood. The objective of this dissertation is to investigate the cardiac impact of EDCs including BPA and BPS, with a focus on their cardiac arrhythmogenesis and underlying cellular and molecular mechanisms. Of particular interest, was to elucidate the signaling cascades and protein targets underlying BPA’s rapid alteration of myocyte Ca2+ handling and promotion of arrhythmogenic-triggered activities in female rodent hearts; and to evaluate how BPS affects cardiac arrhythmogenesis in comparison to BPA. It was demonstrated that protein kinase A (PKA) and Ca2+/Calmodulin-dependent protein kinase II (CAMKII) signaling pathways are the two major signaling pathways activated by BPA. In isolated female rat ventricular myocytes, BPA exposure rapidly increased ii phosphorylation of the ryanodine receptors by PKA but not by CAMKII. BPA exposure also rapidly increased the phosphorylation of phospholamban by CAMKII but not PKA. These two pathways are mediated by estrogen receptor β but not estrogen receptor α, and are shown to be localized. Functional analysis also showed that both PKA and CAMKII were necessary contributors to the arrhythmogenesis of BPA on cardiomyocytes. This study identified the unique signaling cascades of BPA in the heart, and elucidated its novel effects on key Ca2+ handling proteins. Also of interest is the cardiac impact of BPS, especially on the electrical aspect of the heart. It was shown that in female rat hearts, BPS rapidly increased heart rate and promoted ventricular arrhythmias under stress conditions. BPS increased arrhythmogenic-triggered activities in isolated female myocytes via alteration of Ca2+ handling, in particular by increasing spontaneous sarco/endoplasmic reticulum Ca2+ release. BPS exposure increased phosphorylation of two key Ca2+ handling proteins, the ryanodine receptor and phospholamban. Additionally, the pro-arrhythmic effects of BPS were demonstrated to be female-specific, characterized by an inverted-U dose response curve. These results provide important mechanistic insights into the rapid cardiac arrhythmogenesis of BPS in female hearts, and contribute to the evaluation of the potential cardiac toxicity of BPS. Furthermore, the cardiac effects of probenecid were investigated. Collaboratively, it was shown that probenecid increased myocardial contractility using in vivo echocardiography, ex vivo Langendorff perfused heart and isolated myocyte system. The inotropic effect is likely mediated by transient receptor potential vanilloid 2 channels via enhanced sarco/endoplasmic reticulum Ca2+ release. iii iv Acknowledgments First and foremost, I would like to express my deepest gratitude to my thesis advisor, Dr. Hong-Sheng Wang, for being a tremendous mentor for me. Throughout my graduate studies, his careful direction and unwavering support helped me to grow, both academically and personally. His keen sense of science and dedication to research will always influence me in my future career. I am sincerely grateful for his invaluable guidance along this journey. I want to extend my appreciation to the members of my dissertation committee, Drs. Jo El Schultz, Terry Kirley and Steven Kleene, for their insightful advices, constructive criticism and continuous support during my training process. Their constant help with my research and my own progress is indispensible to the completion of this dissertation. My thanks also go to the past and current members of Dr. Hong-Sheng Wang’s laboratory, who are just like my family. I would like to thank Min Dong, Weizhong Song and Sujuan Yan for teaching me key techniques in my projects, Yamei Chen for performing myocyte contractility measurements, Qian Liang and Jianyong Ma for collaborating with me and helping me with troubleshooting, Paul Niklewski for valuable discussions and suggestions. It has been such a pleasure to work with them for all these years, and our friendship will last forever. Special thanks to our collaborator Dr. Jack Rubinstein for his insights and collaborative work in the dissertation. I would like to thank all the faculty and students in the Department of Pharmacology for giving me so much help during my graduate studies. I am truly indebted to Dr. Jo El Schultz, who was our graduate program director, for her constant attention to my study progress and v concern for my personal life. Many thanks to our program coordinator Nancy Thyberg, for always being there to render kind help. I want to thank Janet Manning and Chi Keung Lam for being great teachers for me during my rotations in the first year, and my classmate Clifford Cookman for constant encouragement and support. Finally, my thanks go to my family for their love and continuous support, which have given me strength to overcome the obstacles in both studies and in life. I want to show my appreciation to my parents, for always loving me and believing in me. Especially, I would like to thank my husband Teng, for his unconditional love and being an advocate for every little progress I made. This dissertation would not be completed without his patient help in revision. Lastly, I want to offer gratitude to my baby Aiden, for cheering me up with his beautiful smiles in a tough day, and for helping me to understand the meaning of life. vi Table of Content Page Abstract ..............................................................................................................ii Acknowledgments ............................................................................................v Table of Content .............................................................................................vii List of Abbreviations ........................................................................................xi List of Tables and Figures ...............................................................................xv Chapter I: Introduction .....................................................................................1 1. Environmental endocrine disrupting chemicals ............................................................1 2. Bisphenol A ...................................................................................................................5 3. Bisphenol A and cardiovascular diseases ......................................................................8 4. Cardiac conduction system and ventricular action potential (AP) ...............................10 5. Ventricular arrhythmias and cellular mechanisms .......................................................13 5.1. Premature ventricular beats ................................................................................13 5.2. Ventricular tachycardia ......................................................................................14 5.3. Ventricular fibrillation ........................................................................................16 5.4. Mechanisms of ventricular arrhythmias .............................................................17 5.4.1 Triggered activities: Early after-depolarization and delayed after-depolarization ............................................................................................17 5.4.2 Reentry arrhythmias ..................................................................................18 5.5. Myocyte Ca2+ handling and excitation-contraction coupling .............................20 6. Bisphenol A and cardiac arrhythmias ..........................................................................22 vii 6.1. Experimental evidence .......................................................................................22 6.2. Potential mechanisms ........................................................................................24 7. Bisphenol S ..................................................................................................................27 8. Probenecid ....................................................................................................................29 9. Dissertation focus and hypotheses ...............................................................................31 Chapter II: Materials and Methods ...............................................................35 1. Animals
Recommended publications
  • I LITERATURE-BASED DISCOVERY of KNOWN and POTENTIAL NEW
    LITERATURE-BASED DISCOVERY OF KNOWN AND POTENTIAL NEW MECHANISMS FOR RELATING THE STATUS OF CHOLESTEROL TO THE PROGRESSION OF BREAST CANCER BY YU WANG THESIS Submitted in partial fulfillment of the requirements for the degree of Master of Science in Bioinformatics with a concentration in Library and Information Science in the Graduate College of the University of Illinois at Urbana-Champaign, 2019 Urbana, Illinois Adviser: Professor Vetle I. Torvik Professor Erik Russell Nelson i ABSTRACT Breast cancer has been studied for a long period of time and from a variety of perspectives in order to understand its pathogeny. The pathogeny of breast cancer can be classified into two groups: hereditary and spontaneous. Although cancer in general is considered a genetic disease, spontaneous factors are responsible for most of the pathogeny of breast cancer. In other words, breast cancer is more likely to be caused and deteriorated by the dysfunction of a physical molecule than be caused by germline mutation directly. Interestingly, cholesterol, as one of those molecules, has been discovered to correlate with breast cancer risk. However, the mechanisms of how cholesterol helps breast cancer progression are not thoroughly understood. As a result, this study aims to study known and discover potential new mechanisms regarding to the correlation of cholesterol and breast cancer progression using literature review and literature-based discovery. The known mechanisms are further classified into four groups: cholesterol membrane content, transport of cholesterol, cholesterol metabolites, and other. The potential mechanisms, which are intended to provide potential new treatments, have been identified and checked for feasibility by an expert.
    [Show full text]
  • Masterarbeit / Master's Thesis
    MASTERARBEIT / MASTER’S THESIS Titel der Masterarbeit / Title of the Master‘s Thesis Optimization of an LC-MS/MS Method for the Determination of Xenobiotics in Biological Matrices verfasst von / submitted by Thomas Jamnik BSc angestrebter akademischer Grad / in partial fulfilment of the requirements for the degree of Master of Science (MSc) Wien, 2020 / Vienna 2020 Studienkennzahl lt. Studienblatt / UA 066 863 degree programme code as it appears on the student record sheet: Studienrichtung lt. Studienblatt / Masterstudium Biologische Chemie degree programme as it appears on the student record sheet: Betreut von / Supervisor: Assoz. Prof. Dipl.-Ing. Dr. Benedikt Warth, Bakk.techn. 1 2 Erklärung Ich erkläre, dass die vorliegende Masterarbeit von mit selbst verfasst wurde und ich keine anderen als die angeführten Behelfe verwendet bzw. mich auch sonst keiner unerlaubter Hilfe bedient habe. Ich versichere, dass diese Arbeit bisher weder im In- noch Ausland in irgendeiner Form als Prüfungsarbeit vorgelegt wurde. Ich habe mich bemüht, sämtliche Inhaber der Bildrechte ausfindig zu machen und ihre Zustimmung zur Verwendung der Bilder in dieser Arbeit eingeholt. Sollte dennoch eine Urheberrechtsverletzung bekannt werden, ersuche ich um Meldung bei mir. Danksagung Ich danke Dr. Benedikt Warth nicht nur für die Möglichkeit diese interessante Masterarbeit verfassen zu dürfen, sondern auch für die gewonnenen Erfahrungen die der Einblick in seine Arbeitsgruppe und das Institut für Lebensmittelchemie erlaubt hat. Besonderer Dank gilt meiner direkten Betreuerin Dipl.-Ing. Mira Flasch, welche stets hilfsbereite Unterweisung in die Praxis als auch Theorie der verwendeten Arbeitsmethoden gab, immer für ausgiebige Diskussionen bereit stand und sich viel Zeit für diverse Korrekturen dieser Arbeit nahm.
    [Show full text]
  • Exposure to Endocrine Disruptors During Adulthood: Consequences for Female Fertility
    233 3 S RATTAN and others Endocrine disruptors and 233:3 R109–R129 Review female fertility Exposure to endocrine disruptors during adulthood: consequences for female fertility Saniya Rattan, Changqing Zhou, Catheryne Chiang, Sharada Mahalingam, Correspondence should be addressed Emily Brehm and Jodi A Flaws to J A Flaws Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA Email [email protected] Abstract Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine Key Words disrupting properties in both humans and animals. Female reproduction is an important f endocrine disrupting process, which is regulated by hormones and is susceptible to the effects of exposure chemicals to endocrine disrupting chemicals. Disruptions in female reproductive functions f adult by endocrine disrupting chemicals may result in subfertility, infertility, improper f female hormone production, estrous and menstrual cycle abnormalities, anovulation, and f fertility early reproductive senescence. This review summarizes the effects of a variety of Endocrinology synthetic endocrine disrupting chemicals on fertility during adult life. The chemicals of covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, Journal plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities Journal of Endocrinology in both humans and animals.
    [Show full text]
  • Czech Republic) and Impacts on Quality of Treated Drinking Water
    water Article Pharmaceuticals Load in the Svihov Water Reservoir (Czech Republic) and Impacts on Quality of Treated Drinking Water Josef V. Datel * and Anna Hrabankova T.G. Masaryk Water Research Institute, 16000 Prague, Czech Republic; [email protected] * Correspondence: [email protected]; Tel.: +420-220-197-291 Received: 17 April 2020; Accepted: 6 May 2020; Published: 13 May 2020 Abstract: An important component of micropollutants are PPCPs (pharmaceuticals and personal care products). This paper contains the results of the monitoring of surface water, groundwater and wastewater in the surrounding area of the Svihov drinking water reservoir. Over the period 2017–2019, over 21,000 water samples were taken and analyzed for 112 pharmaceuticals, their metabolites, and other chemicals. The results are discussed in detail for two streams with the highest observed concentration of PPCPs (Hnevkovice, Dolni Kralovice) and two streams with the highest water inflow into the reservoir, representing also the highest mass flow of PPCPs into the reservoir (Miletin, Kacerov). The overall analysis of the results shows that acesulfame, azithromycin, caffeine, gabapentin, hydrochlorothiazide, ibuprofen and its metabolites, oxypurinol, paraxanthine, and saccharin (on some profiles up to tens of thousands ng/dm3) attain the highest concentration and occur most frequently. The evaluation of raw water and treated drinking water quality showed the significant positive effect of water retention in the reservoir (retention time of 413 days) and also of the treatment process, so that the treated drinking water is of high quality and contains only negligible residues of few PPCPs near the detection limit of the analytical method used.
    [Show full text]
  • Endocrine Disruptors
    Endocrine disruptors Afke Groen & Christine Neuhold The RECIPES project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824665 Authors Afke Groen, Maastricht University* Christine Neuhold, Maastricht University * currently works at the think tank Mr. Hans van Mierlo Stichting With thanks to our two anonymous interviewees Manuscript completed in April 2020 Document title WP2 Case study: Endocrine disruptors Work Package WP2 Document Type Deliverable Date 13 April 2020 Document Status Final version Acknowledgments & Disclaimer This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824665. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which might be made of the following information. The views expressed in this publication are the sole responsibility of the author and do not necessarily reflect the views of the European Commission. Reproduction and translation for non-commercial purposes are authorised, provided the source is acknowledged and the publisher is given prior notice and sent a copy. WP2 Case study: Endocrine disruptors i Abstract Endocrine disrupting chemicals (EDCs) are at the centre stage of a scientific and regulatory controversy. Given the complexities, ambiguities and particularly the uncertainties surrounding the hazards of EDCs, the precautionary principle is of utmost relevance to the case. Even the definition of EDCs remains much contested, as do the scientific processes and methods through which to identify them. On the one hand, there is considerable societal pressure to regulate ECDs ‘now’. On the other hand, this quick regulation is often impossible as the limited evidence available does not suffice in the context of traditional EU scientific risk assessment.
    [Show full text]
  • Effects of Bisphenol a and Its Analogs on Reproductive Health: a Mini Review
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE HHS Public Access provided by CDC Stacks Author manuscript Author ManuscriptAuthor Manuscript Author Reprod Manuscript Author Toxicol. Author Manuscript Author manuscript; available in PMC 2019 August 11. Published in final edited form as: Reprod Toxicol. 2018 August ; 79: 96–123. doi:10.1016/j.reprotox.2018.06.005. Effects of Bisphenol A and its Analogs on Reproductive Health: A Mini Review Jacob Steven Siracusa1, Lei Yin1,2, Emily Measel1, Shenuxan Liang1, Xiaozhong Yu1,* 1.Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602 2.ReproTox Biotech LLC, Athens 30602, Georgia Abstract Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analog exposure and reproductive toxicity. It outlines the current state of knowledge on human exposure, toxicokinetics, endocrine activities, and reproductive toxicities of BPA and its analogs. BPA analogs showed similar endocrine potencies when compared to BPA, and emerging data suggest they may pose threats as reproductive hazards in animal models. While evidence based on epidemiological studies is still weak, we have utilized current studies to highlight knowledge gaps and research needs for future risk assessments. Keywords Bisphenol A; Bisphenol F; Bisphenol S; Bisphenol AF; Tetrabromobisphenol A; Reproductive toxicity 1.
    [Show full text]
  • Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer
    International Journal of Molecular Sciences Review Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer Louisane Eve 1,2,3,4,Béatrice Fervers 5,6, Muriel Le Romancer 2,3,4,* and Nelly Etienne-Selloum 1,7,8,* 1 Faculté de Pharmacie, Université de Strasbourg, F-67000 Strasbourg, France; [email protected] 2 Université Claude Bernard Lyon 1, F-69000 Lyon, France 3 Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France 4 CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France 5 Centre de Lutte Contre le Cancer Léon-Bérard, F-69000 Lyon, France; [email protected] 6 Inserm UA08, Radiations, Défense, Santé, Environnement, Center Léon Bérard, F-69000 Lyon, France 7 Service de Pharmacie, Institut de Cancérologie Strasbourg Europe, F-67000 Strasbourg, France 8 CNRS UMR7021/Unistra, Laboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, Université de Strasbourg, F-67000 Strasbourg, France * Correspondence: [email protected] (M.L.R.); [email protected] (N.E.-S.); Tel.: +33-4-(78)-78-28-22 (M.L.R.); +33-3-(68)-85-43-28 (N.E.-S.) Received: 27 October 2020; Accepted: 25 November 2020; Published: 30 November 2020 Abstract: 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.
    [Show full text]
  • 2019 Minnesota Chemicals of High Concern List
    Minnesota Department of Health, Chemicals of High Concern List, 2019 Persistent, Bioaccumulative, Toxic (PBT) or very Persistent, very High Production CAS Bioaccumulative Use Example(s) and/or Volume (HPV) Number Chemical Name Health Endpoint(s) (vPvB) Source(s) Chemical Class Chemical1 Maine (CA Prop 65; IARC; IRIS; NTP Wood and textiles finishes, Cancer, Respiratory 11th ROC); WA Appen1; WA CHCC; disinfection, tissue 50-00-0 Formaldehyde x system, Eye irritant Minnesota HRV; Minnesota RAA preservative Gastrointestinal Minnesota HRL Contaminant 50-00-0 Formaldehyde (in water) system EU Category 1 Endocrine disruptor pesticide 50-29-3 DDT, technical, p,p'DDT Endocrine system Maine (CA Prop 65; IARC; IRIS; NTP PAH (chem-class) 11th ROC; OSPAR Chemicals of Concern; EuC Endocrine Disruptor Cancer, Endocrine Priority List; EPA Final PBT Rule for 50-32-8 Benzo(a)pyrene x x system TRI; EPA Priority PBT); Oregon P3 List; WA Appen1; Minnesota HRV WA Appen1; Minnesota HRL Dyes and diaminophenol mfg, wood preservation, 51-28-5 2,4-Dinitrophenol Eyes pesticide, pharmaceutical Maine (CA Prop 65; IARC; NTP 11th Preparation of amino resins, 51-79-6 Urethane (Ethyl carbamate) Cancer, Development ROC); WA Appen1 solubilizer, chemical intermediate Maine (CA Prop 65; IARC; IRIS; NTP Research; PAH (chem-class) 11th ROC; EPA Final PBT Rule for 53-70-3 Dibenzo(a,h)anthracene Cancer x TRI; WA PBT List; OSPAR Chemicals of Concern); WA Appen1; Oregon P3 List Maine (CA Prop 65; NTP 11th ROC); Research 53-96-3 2-Acetylaminofluorene Cancer WA Appen1 Maine (CA Prop 65; IARC; IRIS; NTP Lubricant, antioxidant, 55-18-5 N-Nitrosodiethylamine Cancer 11th ROC); WA Appen1 plastics stabilizer Maine (CA Prop 65; IRIS; NTP 11th Pesticide (EPA reg.
    [Show full text]
  • CAS 80-09-1 Bisphenol S (BPS)
    CAS 80-09-1 Bisphenol S (BPS) Toxicity EPA classified BPS as a high hazard for toxicity for repeated exposures and as a moderate hazard for developmental and reproductive toxicity based on a study in which rats produced fewer live offspring, adverse liver effects, longer estrous cycle, and showed a decreased fertility index.1 A dose-dependent increase in focal squamous cell metaplasia of glandular epithelium in the uterus of female rats and atrophy of mammary glands in male rats after 90-days was observed.2 In vitro assays have shown BPS can bind with estrogen receptors to induce cell proliferation or inhibit androgenic activity of dihydrotestosterone.3 Exposure BPS was detected through biomonitoring in 81% of human urine sampled from 2010- 2011 in several Asian countries and the U.S.4 A 2000-2014 biomonitoring study of U.S. adults detected BPS in urine samples more frequently over time, from 25% in 2000, to 75% in 2014.5 BPS was detected in various foods gathered in 2008-2010 from an Albany, New York grocery store which included meats, seafood, fruit and vegetables.6 BPS was detected in the breast milk of French women in a 2015 study.7 A New York study detected BPS in house dust samples gathered between 2006-2010.8 BPS was primarily used in polymer production and thermal papers as a substitute for BPA. BPS has been detected in personal care products, polyethersulfone (PES) plastics used in baby bottles, sales receipt paper, and other paper products.3,8-12 References 1. U.S. Environmental Protection Agency (EPA).
    [Show full text]
  • Endocrine Disruptors and Biodiversity Biological Diversity Faced with Chemical Risks : the Need for a Paradigm Shi
    © TONY CAMPBELL / PHO CAMPBELL TONY © T OXPRESS REPORT 2011 Conservation Biodiversity Sustainability Endocrine disruptors and biodiversity biological diversity faced with chemical risks : the need for a paradigm shi page 1 WWF WWF is one of the world’s largest and most experienced independent conservation organizations, with over 5 mil- lion supporters and a global network active in more than 100 countries. WWF’s mission is to stop the degradation of the planet’s natural environment and to build a future in which humans live in harmony with nature, by conserving the world’s bio- logical diversity, ensuring that the use of renewable natural resources is sustainable, and promoting the reduction of pollution and wasteful consumption. Concept & design by © ArthurSteenHorneAdamson Contributors Editors in chief, Kévin Jean and Tarik Benmarhnia Editorial team, JC Lefeuvre, H. Roche, A. Cicolella, C. Deshayes Translation team, Ash Browning, Margie Rynn, Olivia Delas Layout, Roland Niccoli, Openscop © 1986 Panda Symbol WWF - World Wide Fund For nature (Formerly World Wildlife Fund) ® “WWF” & “living planet” are WWF Registered Trademarks / “WWF” & “Pour une planète vivante” sont des marques déposées. WWF France. 1 carrefour de Longchamp. 75016 Paris. www.wwf.fr Endocrine disruptors & biodiversity : the need for a paradigm shift TABLE OF CONTENTS PART I : CONTEXT AND GENERAL Details OF ENDOCRINE DISRUPTORS 5 Definitions and general context 5 ED categorization 6 A significant environmental challenge 8 A few regulations 9 PART II : EDS IN THE ENVIRONMENT 10 Main sources of contamination 10 How EDs function in the environment – today and in the future 17 PART III : ThE EFFECTS OF EDS ON LIVING BEINGS 18 how much we know and where to go from here The extent of the ED problem 18 Towards a new approach of EDs 22 CONCLUSION 27 BIBLIOGRAPHY 28 page 3 page 3 © E ZEQUIEL ZEQUIEL S 18 CAGNE TT Minimal number of man-made I / WWF- chemicals found in the blood of 13 families from 12 European C countries during WWF’s 2005 ANON Detox campaign.
    [Show full text]
  • Full Version (PDF File)
    Physiol. Res. 68: 689-693, 2019 https://doi.org/10.33549/physiolres.934200 SHORT COMMUNICATION Assessment of the Effective Impact of Bisphenols on Mitochondrial Activity and Steroidogenesis in a Dose-Dependency in Mice TM3 Leydig Cells T. JAMBOR1, E. KOVACIKOVA2, H. GREIFOVA1, A. KOVACIK1, L. LIBOVA3, N. LUKAC1 1Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic, 2AgroBioTech Research Centre, Slovak University of Agriculture in Nitra, Nitra, Slovak Republic, 3Faculty of Health and Social Work St. Ladislav, St. Elisabeth University of Health Care and Social Work, Bratislava, Slovak Republic Received May 3, 2019 Accepted June 24, 2019 Epub Ahead of Print July 25, 2019 Summary Biotechnology and Food Sciences, Slovak University of Agriculture The increasing worldwide production of bisphenols has been in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovak Republic. E-mail: associated to several human diseases, such as chronic respiratory [email protected] and kidney diseases, diabetes, breast cancer, prostate cancer, behavioral troubles and reproductive disorders in both sexes. The Bisphenol A (BPA, 2,2-bis[4-hydroxyphenyl] aim of the present in vitro study was to evaluate the potential propane) is one of the oldest and most studied synthetic impact bisphenols A, B, S and F on the cell viability and substance known as an endocrine disruptor (ED). About testosterone release in TM3 Leydig cell line. Mice Leydig cells 70 % of BPA production is used to produce were cultured in the presence of different concentrations of polycarbonate plastics used in a variety of common bisphenols (0.04-50 µg.ml-1) during 24 h exposure.
    [Show full text]
  • Phytoestrogens in Foods in the Nordic Market
    TemaNord 2017:541 Phytoestrogens in foods on the Nordic market the Nordic on foods in 2017:541 Phytoestrogens TemaNord Nordic Council of Ministers Nordens Hus Ved Stranden 18 DK-1061 Copenhagen K www.norden.org Phytoestrogens in foods on the Nordic market Phytoestrogens are plant-derived compounds that may bind to estrogen receptors, but with less affinity than the natural ligand estradiol. They may be biologically active as such or after metabolization in our body. To investigate the occurrence and level of phytoestrogens, scientific literature was screened for data on isoflavones, lignans, stilbenes and coumestans in raw and processed foods of plant origin. The review presents data based both on analytical methods hydrolysing glucosides and non-destructive methods. Many phytoestrogens are phytoalexins. Their production is induced when plants are exposed to abiotic and/or biotic stress. This could explain the rather different levels reported in plants by various investigators, and indicates that many samples are required to describe the levels generally occurring in foodstuffs. The influence of food processing was also considered. Phytoestrogens in foods on the Nordic market A literature review on occurrence and levels Phytoestrogens in foods on the Nordic market A literature review on occurrence and levels Linus Carlsson Forslund and Hans Christer Andersson TemaNord 2017:541 Phytoestrogens in foods on the Nordic market A literature review on occurrence and levels Linus Carlsson Forslund and Hans Christer Andersson ISBN 978-92-893-5046-4 (PRINT) ISBN 978-92-893-5047-1 (PDF) ISBN 978-92-893-5048-8 (EPUB) http://dx.doi.org/10.6027/TN2017-541 TemaNord 2017:541 ISSN 0908-6692 Standard: PDF/UA-1 ISO 14289-1 © Nordic Council of Ministers 2017 Cover photo: Unsplash.com Print: Rosendahls Printed in Denmark Although the Nordic Council of Ministers funded this publication, the contents do not necessarily reflect its views, policies or recommendations.
    [Show full text]