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      Call for Papers: Epidemiology and Health Impacts of Neuroendocrine Tumors

      Submit here before August 30, 2024

      About Neuroendocrinology: 3.2 Impact Factor I 8.3 CiteScore I 1.009 Scimago Journal & Country Rank (SJR)

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      A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer

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          Abstract

          During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.

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          Most cited references44

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          Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism.

          Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.
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            Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.

            The increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. The results suggest that abnormalities in male sex development induced by p,p'-DDE and related environmental chemicals may be mediated at the level of the androgen receptor.
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              Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union.

              Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-318-05971-7
                978-3-318-05972-4
                1663-2818
                1663-2826
                2016
                November 2016
                13 February 2016
                : 86
                : 4
                : 240-246
                Affiliations
                University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
                Author notes
                *Niels E. Skakkebaek, University Department of Growth and Reproduction, Rigshospitalet section 5064, Blegdamsvej 9, DK-2100 Copenhagen (Denmark), E-Mail nes@rh.dk
                Article
                443400 Horm Res Paediatr 2016;86:240-246
                10.1159/000443400
                26871895
                2e5d7e51-4ba6-4b8e-a2af-f89341844495
                © 2016 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 10 November 2015
                : 16 December 2015
                Page count
                Figures: 3, References: 74, Pages: 7
                Categories
                Mini Review

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Testicular dysgenesis syndrome,Cryptorchidism,Reproduction,Testicular cancer,Endocrine disrupters,Hypospadias

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