In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life
Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants that interfere with the endocrine system, resulting in developmental malformations, reproductive disorders, and alterations to immune and nervous system function. The emergence of screening studies identifying these chemica...
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Veröffentlicht in: | Environmental research 2022-01, Vol.203, p.111829-111829, Article 111829 |
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description | Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants that interfere with the endocrine system, resulting in developmental malformations, reproductive disorders, and alterations to immune and nervous system function. The emergence of screening studies identifying these chemicals in fetal developmental matrices such as maternal blood, placenta and amniotic fluid has steered research focus towards elucidation of in utero effects of exposure to these chemicals, as their capacity to cross the placenta and reach the fetus was established. The presence of EDCs, a majority of which are estrogen mimics, in the fetal environment during early development could potentially affect neurodevelopment, with implications for behavioural and neurological disorders in adult life. This review summarizes studies in animal models and human cohorts that aim to elucidate mechanisms of action of EDCs in the context of neurodevelopment and disease risk in adult life. This is a significant area of study as early brain development is heavily mediated by estrogen and could be particularly sensitive to EDC exposure. A network analysis presented using genes summarized in this review, further show a significant association with disorders such as major depressive disorder, alcoholic disorder, psychotic disorders and autism spectrum disorder. Functional outcomes such as alterations in memory, behaviour, cognition, learning memory, feeding behaviour and regulation of ion transport are also highlighted. Interactions between genes, receptors and signaling pathways like NMDA glutamate receptor activity, 5-hydroxytryptamine receptor activity, Ras-activated Ca2+ influx and Grin2A interactions, provide further potential mechanisms of action of EDCs in mediating brain function. Taken together with the growing pool of human and animal studies, this review summarizes current status of EDC neurotoxicity research, limitations and future directions of study for researchers.
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•Sex-specific neurotoxicity in EDC-exposed offspring underlie adult disease susceptibility.•Prenatal EDC exposure impairs signaling pathways associated with neurological disorders.•Network analysis highlights targets for mechanistic elucidation of EDC neurotoxicity. |
doi_str_mv | 10.1016/j.envres.2021.111829 |
format | Article |
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[Display omitted]
•Sex-specific neurotoxicity in EDC-exposed offspring underlie adult disease susceptibility.•Prenatal EDC exposure impairs signaling pathways associated with neurological disorders.•Network analysis highlights targets for mechanistic elucidation of EDC neurotoxicity.</description><identifier>ISSN: 0013-9351</identifier><identifier>EISSN: 1096-0953</identifier><identifier>DOI: 10.1016/j.envres.2021.111829</identifier><identifier>PMID: 34358505</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Autism Spectrum Disorder ; Behavioural disorders ; Depressive Disorder, Major ; Developmental neurotoxicity ; Endocrine disruption ; Endocrine Disruptors - toxicity ; Female ; Fetal development ; Humans ; Intrauterine environment ; Nervous System Diseases - chemically induced ; Neurological disorders ; Pregnancy ; Reproduction</subject><ispartof>Environmental research, 2022-01, Vol.203, p.111829-111829, Article 111829</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-d440c07524da57097f1358358d8fd3b81c61f80a989162c7fdc9d5f812f41ecb3</citedby><cites>FETCH-LOGICAL-c362t-d440c07524da57097f1358358d8fd3b81c61f80a989162c7fdc9d5f812f41ecb3</cites><orcidid>0000-0002-7672-8597</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.envres.2021.111829$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34358505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raja, Glancis Luzeena</creatorcontrib><creatorcontrib>Subhashree, K. Divya</creatorcontrib><creatorcontrib>Kantayya, Kamalini Esther</creatorcontrib><title>In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life</title><title>Environmental research</title><addtitle>Environ Res</addtitle><description>Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants that interfere with the endocrine system, resulting in developmental malformations, reproductive disorders, and alterations to immune and nervous system function. The emergence of screening studies identifying these chemicals in fetal developmental matrices such as maternal blood, placenta and amniotic fluid has steered research focus towards elucidation of in utero effects of exposure to these chemicals, as their capacity to cross the placenta and reach the fetus was established. The presence of EDCs, a majority of which are estrogen mimics, in the fetal environment during early development could potentially affect neurodevelopment, with implications for behavioural and neurological disorders in adult life. This review summarizes studies in animal models and human cohorts that aim to elucidate mechanisms of action of EDCs in the context of neurodevelopment and disease risk in adult life. This is a significant area of study as early brain development is heavily mediated by estrogen and could be particularly sensitive to EDC exposure. A network analysis presented using genes summarized in this review, further show a significant association with disorders such as major depressive disorder, alcoholic disorder, psychotic disorders and autism spectrum disorder. Functional outcomes such as alterations in memory, behaviour, cognition, learning memory, feeding behaviour and regulation of ion transport are also highlighted. Interactions between genes, receptors and signaling pathways like NMDA glutamate receptor activity, 5-hydroxytryptamine receptor activity, Ras-activated Ca2+ influx and Grin2A interactions, provide further potential mechanisms of action of EDCs in mediating brain function. Taken together with the growing pool of human and animal studies, this review summarizes current status of EDC neurotoxicity research, limitations and future directions of study for researchers.
[Display omitted]
•Sex-specific neurotoxicity in EDC-exposed offspring underlie adult disease susceptibility.•Prenatal EDC exposure impairs signaling pathways associated with neurological disorders.•Network analysis highlights targets for mechanistic elucidation of EDC neurotoxicity.</description><subject>Animals</subject><subject>Autism Spectrum Disorder</subject><subject>Behavioural disorders</subject><subject>Depressive Disorder, Major</subject><subject>Developmental neurotoxicity</subject><subject>Endocrine disruption</subject><subject>Endocrine Disruptors - toxicity</subject><subject>Female</subject><subject>Fetal development</subject><subject>Humans</subject><subject>Intrauterine environment</subject><subject>Nervous System Diseases - chemically induced</subject><subject>Neurological disorders</subject><subject>Pregnancy</subject><subject>Reproduction</subject><issn>0013-9351</issn><issn>1096-0953</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-KFDEQxoO4uOPqG4jk6KXHJN3p6XgQZHF1YMGLnkMmqWiGdNLmz7D7FvvIZrZXj0KgUvD7vqLqQ-gNJVtK6Pj-uIVwSpC3jDC6pZROTDxDG0rE2BHB--doQwjtO9Fzeole5nxsLeU9eYEu-6HnEyd8gx72AdcCKWK4W2KuCXBp_2CiTi4ANi6nupSYMlbBYAMn8HGZIRTlcYCaYol3Trty_wHv58U7rYqLIWMbEz7AL3VysabGntWPvI8_G-TPzjEZaMYuYGWqL9g7C6_QhVU-w-uneoV-3Hz-fv21u_32ZX_96bbT_chKZ4aBaLLjbDCK74jYWdpWas9M1vSHieqR2okoMQk6Mr2zRgvD7USZHSjoQ3-F3q2-S4q_K-QiZ5c1eK8CxJol41wMjItRNHRYUZ1izgmsXJKbVbqXlMhzFvIo1yzkOQu5ZtFkb58m1MMM5p_o7_Eb8HEFoO15cpBk1g6CBuMS6CJNdP-f8AcDf6B1</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Raja, Glancis Luzeena</creator><creator>Subhashree, K. Divya</creator><creator>Kantayya, Kamalini Esther</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7672-8597</orcidid></search><sort><creationdate>202201</creationdate><title>In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life</title><author>Raja, Glancis Luzeena ; Subhashree, K. Divya ; Kantayya, Kamalini Esther</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-d440c07524da57097f1358358d8fd3b81c61f80a989162c7fdc9d5f812f41ecb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Autism Spectrum Disorder</topic><topic>Behavioural disorders</topic><topic>Depressive Disorder, Major</topic><topic>Developmental neurotoxicity</topic><topic>Endocrine disruption</topic><topic>Endocrine Disruptors - toxicity</topic><topic>Female</topic><topic>Fetal development</topic><topic>Humans</topic><topic>Intrauterine environment</topic><topic>Nervous System Diseases - chemically induced</topic><topic>Neurological disorders</topic><topic>Pregnancy</topic><topic>Reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raja, Glancis Luzeena</creatorcontrib><creatorcontrib>Subhashree, K. Divya</creatorcontrib><creatorcontrib>Kantayya, Kamalini Esther</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raja, Glancis Luzeena</au><au>Subhashree, K. Divya</au><au>Kantayya, Kamalini Esther</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life</atitle><jtitle>Environmental research</jtitle><addtitle>Environ Res</addtitle><date>2022-01</date><risdate>2022</risdate><volume>203</volume><spage>111829</spage><epage>111829</epage><pages>111829-111829</pages><artnum>111829</artnum><issn>0013-9351</issn><eissn>1096-0953</eissn><abstract>Endocrine disrupting chemicals (EDCs) are a class of environmental toxicants that interfere with the endocrine system, resulting in developmental malformations, reproductive disorders, and alterations to immune and nervous system function. The emergence of screening studies identifying these chemicals in fetal developmental matrices such as maternal blood, placenta and amniotic fluid has steered research focus towards elucidation of in utero effects of exposure to these chemicals, as their capacity to cross the placenta and reach the fetus was established. The presence of EDCs, a majority of which are estrogen mimics, in the fetal environment during early development could potentially affect neurodevelopment, with implications for behavioural and neurological disorders in adult life. This review summarizes studies in animal models and human cohorts that aim to elucidate mechanisms of action of EDCs in the context of neurodevelopment and disease risk in adult life. This is a significant area of study as early brain development is heavily mediated by estrogen and could be particularly sensitive to EDC exposure. A network analysis presented using genes summarized in this review, further show a significant association with disorders such as major depressive disorder, alcoholic disorder, psychotic disorders and autism spectrum disorder. Functional outcomes such as alterations in memory, behaviour, cognition, learning memory, feeding behaviour and regulation of ion transport are also highlighted. Interactions between genes, receptors and signaling pathways like NMDA glutamate receptor activity, 5-hydroxytryptamine receptor activity, Ras-activated Ca2+ influx and Grin2A interactions, provide further potential mechanisms of action of EDCs in mediating brain function. Taken together with the growing pool of human and animal studies, this review summarizes current status of EDC neurotoxicity research, limitations and future directions of study for researchers.
[Display omitted]
•Sex-specific neurotoxicity in EDC-exposed offspring underlie adult disease susceptibility.•Prenatal EDC exposure impairs signaling pathways associated with neurological disorders.•Network analysis highlights targets for mechanistic elucidation of EDC neurotoxicity.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>34358505</pmid><doi>10.1016/j.envres.2021.111829</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-7672-8597</orcidid></addata></record> |
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subjects | Animals Autism Spectrum Disorder Behavioural disorders Depressive Disorder, Major Developmental neurotoxicity Endocrine disruption Endocrine Disruptors - toxicity Female Fetal development Humans Intrauterine environment Nervous System Diseases - chemically induced Neurological disorders Pregnancy Reproduction |
title | In utero exposure to endocrine disruptors and developmental neurotoxicity: Implications for behavioural and neurological disorders in adult life |
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