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      Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

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          Abstract

          Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

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          Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004

          Background Exposure to chemicals during fetal development can increase the risk of adverse health effects, and while biomonitoring studies suggest pregnant women are exposed to chemicals, little is known about the extent of multiple chemicals exposures among pregnant women in the United States. Objective We analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. Methods We analyzed data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003–2004, a nationally representative sample of the U.S. population. For each chemical analyte, we calculated descriptive statistics. We calculated the number of chemicals detected within the following chemical classes: polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), organochlorine pesticides, and phthalates and across multiple chemical classes. We compared chemical analyte concentrations for pregnant and nonpregnant women using least-squares geometric means, adjusting for demographic and physiological covariates. Results The percentage of pregnant women with detectable levels of an individual chemical ranged from 0 to 100%. Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons, and perchlorate were detected in 99–100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes. We found, generally, that levels in pregnant women were similar to or lower than levels in nonpregnant women; adjustment for covariates tended to increase levels in pregnant women compared with nonpregnant women. Conclusions Pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy making.
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            Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

            Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.
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              Early-life exposure to EDCs: role in childhood obesity and neurodevelopment

              Endocrine-disrupting chemicals (EDCs) can increase the risk of childhood diseases by disrupting hormone-mediated processes critical for growth and development. Here, Joseph Braun discusses epidemiological evidence of associations between early-life exposure to EDCs and childhood neurodevelopmental disorders and obesity.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 June 2018
                June 2018
                : 19
                : 6
                : 1647
                Affiliations
                [1 ]Department of Obstetrics, Gynaecology and Paediatrics, Azienda USL-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy; cecilia.catellani@ 123456ausl.re.it (C.C.); francesca.cirillo@ 123456ausl.re.it (F.C.); giancarlo.gargano@ 123456ausl.re.it (G.G.); pietro.lazzeroni@ 123456ausl.re.it (P.L.); chiara.sartori@ 123456ausl.re.it (C.S.); gabriele.tridenti@ 123456ausl.re.it (G.T.); sergio.amarri@ 123456ausl.re.it (S.A.)
                [2 ]Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy; s.angelini@ 123456unibo.it
                [3 ]Former Department of Medicine, University of Parma, Via A. Catalani 10, 43123 Parma, Italy; sbernasconi@ 123456gmail.com
                [4 ]ECERI European Cancer and Environment Research Institute, Square de Meeus, 38-40, 1000 Bruxelles, Belgium; erburg@ 123456libero.it
                [5 ]Pediatric Endocrinology Programme, Pediatrics Unit, Department of Woman, Child Health and Urologic Diseases, AOU S. Orsola-Malpighi, Via Massarenti, 11, 40138 Bologna, Italy; alessandra.cassio@ 123456unibo.it
                [6 ]Department of Pediatrics (DPUO), Bambino Gesù Children’s Hospital, Tor Vergata University, Piazza S. Onofrio 4, 00165 Rome, Italy; annalisa.deodati@ 123456opbg.net
                [7 ]Department of Pediatrics and Neonatology, Augusto Murri Hospital, Via Augusto Murri, 17, 63900 Fermo, Itlay; enrica.fabbrizi@ 123456libero.it
                [8 ]Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section, AOU and University of Cagliari, via Ospedale, 54, 09124 Cagliari, Italy; vafanos@ 123456tiscali.it
                [9 ]Villa Santa Maria Institute, Neuropsychiatric Rehabilitation Center, Via IV Novembre 15, 22038 Tavernerio (Como), Italy; enzo.grossi@ 123456bracco.com
                [10 ]Department of Medical and Surgical Sciences of the Mother, Children and Adults, Pediatrics Unit, University of Modena and Reggio Emilia, via del Pozzo, 71, 41124 Modena, Italy; lorenzo.iughetti@ 123456unimore.it (L.I.); barbara.predieri@ 123456unimore.it (B.P.)
                [11 ]Department of Veterinary Public Health and Food Safety, Food and Veterinary Toxicology Unit ISS–National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy; alberto.mantovani@ 123456iss.it
                [12 ]Department of Traslational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 55, 56123 Pisa, Italy; lucia.migliore@ 123456med.unipi.it
                [13 ]Unit of Neuroscience, Department of Medicine and Surgery, University of Parma, Via Gramsci, 14, 43126 Parma, Italy; paola.palanza@ 123456unipr.it
                [14 ]Laboratory of Neuroendocrinology, Department of Neuroscience Rita Levi Montalcini, University of Turin, Via Cherasco 15, 10126 Turin, Italy; giancarlo.panzica@ 123456unito.it
                [15 ]Neuroscience Institute Cavalieri-Ottolenghi (NICO), Regione Gonzole, 10, 10043 Orbassano (Turin), Italy
                [16 ]Department of Chemistry ‘Ugo Schiff’, University of Florence, Via della Lastruccia, 3-13, 50019 Sesto Fiorentino, Florence, Italy; annamaria.papini@ 123456unifi.it
                [17 ]Unit of Evolutionary and Functional Biology—Department of Chemistry, Life Sciences and Environmental Sustainability (SCVSA)-University of Parma–11/a, 43124 Parma, Italy; stefano.parmigiani@ 123456unipr.it
                Author notes
                [* ]Correspondence: mariaelisabeth.street@ 123456ausl.re.it ; Tel.: +39-0522-296194; Fax: +39-0522-296266
                Author information
                https://orcid.org/0000-0001-8427-8971
                https://orcid.org/0000-0002-1609-0421
                https://orcid.org/0000-0002-6354-9979
                https://orcid.org/0000-0001-5602-0316
                https://orcid.org/0000-0003-0370-7872
                https://orcid.org/0000-0003-2873-4260
                https://orcid.org/0000-0002-9302-4647
                https://orcid.org/0000-0002-2947-7107
                https://orcid.org/0000-0002-3302-6886
                Article
                ijms-19-01647
                10.3390/ijms19061647
                6032228
                29865233
                ceba5a11-8bc9-40de-8c93-e6e043b86483
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 April 2018
                : 31 May 2018
                Categories
                Review

                Molecular biology
                endocrine disrupting chemicals (edcs),neurodevelopment,autism,obesity,puberty,fertility,thyroid function,epigenetics,carcinogenesis,growth

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