Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish
The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but d...
Gespeichert in:
| Veröffentlicht in: | Environmental science & technology 2019-01, Vol.53 (1), p.463-474 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 474 |
|---|---|
| container_issue | 1 |
| container_start_page | 463 |
| container_title | Environmental science & technology |
| container_volume | 53 |
| creator | Brown, A. Ross Green, Jon M Moreman, John Gunnarsson, Lina M Mourabit, Sulayman Ball, Jonathan Winter, Matthew J Trznadel, Maciej Correia, Ana Hacker, Christian Perry, Alexis Wood, Mark E Hetheridge, Malcolm J Currie, Richard A Tyler, Charles R |
| description | The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states. |
| doi_str_mv | 10.1021/acs.est.8b04281 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6333396</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2189550795</sourcerecordid><originalsourceid>FETCH-LOGICAL-a490t-20b0474fb7b2d708e5850fabd6b4e88283c605362988a87bee481319577feafe3</originalsourceid><addsrcrecordid>eNp1kcFrFDEYxYNY7Fo9e5OAF0Fm-yWZyWQuQrvUWuiihxbES0hmvrgps5M1mSn0v2_W3S5aMJdA8nvvy8sj5B2DOQPOTk2b5pjGubJQcsVekBmrOBSVqthLMgNgomiE_HFMXqd0BwBcgHpFjgVkSgo-I3ZhYufDvUnt1JtIL5zDdkzUDB1dhh53p0tsV2bwaZ1ocPTcp80Kh9DTsz_cVeaXOBobej8iXZ5_p36gP9FG43xavSFHzvQJ3-73E3L75eJm8bW4_nZ5tTi7LkzZwFhwyBnq0tna8q4GhTkEOGM7aUtUiivRSqiE5I1SRtUWsVRMsKaqa4fGoTghn3e-m8musWtxGKPp9Sb6tYkPOhiv_70Z_Er_CvdairwamQ0-7g1i-D3lb9Vrn1rsezNgmJLmTDVVBXVTZfTDM_QuTHHI8TIllVKMS8jU6Y5qY0gpojs8hoHe9qdzf3qr3veXFe__znDgnwrLwKcdsFUeZv7P7hFIc6YU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2168881260</pqid></control><display><type>article</type><title>Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish</title><source>American Chemical Society</source><source>MEDLINE</source><creator>Brown, A. Ross ; Green, Jon M ; Moreman, John ; Gunnarsson, Lina M ; Mourabit, Sulayman ; Ball, Jonathan ; Winter, Matthew J ; Trznadel, Maciej ; Correia, Ana ; Hacker, Christian ; Perry, Alexis ; Wood, Mark E ; Hetheridge, Malcolm J ; Currie, Richard A ; Tyler, Charles R</creator><creatorcontrib>Brown, A. Ross ; Green, Jon M ; Moreman, John ; Gunnarsson, Lina M ; Mourabit, Sulayman ; Ball, Jonathan ; Winter, Matthew J ; Trznadel, Maciej ; Correia, Ana ; Hacker, Christian ; Perry, Alexis ; Wood, Mark E ; Hetheridge, Malcolm J ; Currie, Richard A ; Tyler, Charles R</creatorcontrib><description>The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states.</description><identifier>ISSN: 0013-936X</identifier><identifier>ISSN: 1520-5851</identifier><identifier>EISSN: 1520-5851</identifier><identifier>DOI: 10.1021/acs.est.8b04281</identifier><identifier>PMID: 30520632</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animal models ; Animals ; Aortic valve ; Benzhydryl Compounds ; Biomarkers ; Bisphenol A ; Blood flow ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular system ; Chemicals ; Child ; Children ; Collagen ; Computer simulation ; Curvature ; Danio rerio ; Embryos ; Environmental science ; Estrogens ; Exposure ; Extracellular matrix ; Fetuses ; Fluorescence ; Heart ; heart valve diseases ; Heart valves ; Histopathology ; Humans ; Metabolites ; Molecular modelling ; Organic chemistry ; Phenols ; Rheumatic heart disease ; Structural integrity ; tissues ; transcriptomics ; Ventricle ; Wildlife ; Xenoestrogens ; Zebrafish</subject><ispartof>Environmental science & technology, 2019-01, Vol.53 (1), p.463-474</ispartof><rights>Copyright American Chemical Society Jan 2, 2019</rights><rights>Copyright © 2018 American Chemical Society 2018 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a490t-20b0474fb7b2d708e5850fabd6b4e88283c605362988a87bee481319577feafe3</citedby><cites>FETCH-LOGICAL-a490t-20b0474fb7b2d708e5850fabd6b4e88283c605362988a87bee481319577feafe3</cites><orcidid>0000-0002-3892-8993</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.est.8b04281$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.est.8b04281$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,777,781,882,2752,27057,27905,27906,56719,56769</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30520632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, A. Ross</creatorcontrib><creatorcontrib>Green, Jon M</creatorcontrib><creatorcontrib>Moreman, John</creatorcontrib><creatorcontrib>Gunnarsson, Lina M</creatorcontrib><creatorcontrib>Mourabit, Sulayman</creatorcontrib><creatorcontrib>Ball, Jonathan</creatorcontrib><creatorcontrib>Winter, Matthew J</creatorcontrib><creatorcontrib>Trznadel, Maciej</creatorcontrib><creatorcontrib>Correia, Ana</creatorcontrib><creatorcontrib>Hacker, Christian</creatorcontrib><creatorcontrib>Perry, Alexis</creatorcontrib><creatorcontrib>Wood, Mark E</creatorcontrib><creatorcontrib>Hetheridge, Malcolm J</creatorcontrib><creatorcontrib>Currie, Richard A</creatorcontrib><creatorcontrib>Tyler, Charles R</creatorcontrib><title>Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish</title><title>Environmental science & technology</title><addtitle>Environ. Sci. Technol</addtitle><description>The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states.</description><subject>Animal models</subject><subject>Animals</subject><subject>Aortic valve</subject><subject>Benzhydryl Compounds</subject><subject>Biomarkers</subject><subject>Bisphenol A</subject><subject>Blood flow</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular system</subject><subject>Chemicals</subject><subject>Child</subject><subject>Children</subject><subject>Collagen</subject><subject>Computer simulation</subject><subject>Curvature</subject><subject>Danio rerio</subject><subject>Embryos</subject><subject>Environmental science</subject><subject>Estrogens</subject><subject>Exposure</subject><subject>Extracellular matrix</subject><subject>Fetuses</subject><subject>Fluorescence</subject><subject>Heart</subject><subject>heart valve diseases</subject><subject>Heart valves</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Metabolites</subject><subject>Molecular modelling</subject><subject>Organic chemistry</subject><subject>Phenols</subject><subject>Rheumatic heart disease</subject><subject>Structural integrity</subject><subject>tissues</subject><subject>transcriptomics</subject><subject>Ventricle</subject><subject>Wildlife</subject><subject>Xenoestrogens</subject><subject>Zebrafish</subject><issn>0013-936X</issn><issn>1520-5851</issn><issn>1520-5851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFrFDEYxYNY7Fo9e5OAF0Fm-yWZyWQuQrvUWuiihxbES0hmvrgps5M1mSn0v2_W3S5aMJdA8nvvy8sj5B2DOQPOTk2b5pjGubJQcsVekBmrOBSVqthLMgNgomiE_HFMXqd0BwBcgHpFjgVkSgo-I3ZhYufDvUnt1JtIL5zDdkzUDB1dhh53p0tsV2bwaZ1ocPTcp80Kh9DTsz_cVeaXOBobej8iXZ5_p36gP9FG43xavSFHzvQJ3-73E3L75eJm8bW4_nZ5tTi7LkzZwFhwyBnq0tna8q4GhTkEOGM7aUtUiivRSqiE5I1SRtUWsVRMsKaqa4fGoTghn3e-m8musWtxGKPp9Sb6tYkPOhiv_70Z_Er_CvdairwamQ0-7g1i-D3lb9Vrn1rsezNgmJLmTDVVBXVTZfTDM_QuTHHI8TIllVKMS8jU6Y5qY0gpojs8hoHe9qdzf3qr3veXFe__znDgnwrLwKcdsFUeZv7P7hFIc6YU</recordid><startdate>20190102</startdate><enddate>20190102</enddate><creator>Brown, A. Ross</creator><creator>Green, Jon M</creator><creator>Moreman, John</creator><creator>Gunnarsson, Lina M</creator><creator>Mourabit, Sulayman</creator><creator>Ball, Jonathan</creator><creator>Winter, Matthew J</creator><creator>Trznadel, Maciej</creator><creator>Correia, Ana</creator><creator>Hacker, Christian</creator><creator>Perry, Alexis</creator><creator>Wood, Mark E</creator><creator>Hetheridge, Malcolm J</creator><creator>Currie, Richard A</creator><creator>Tyler, Charles R</creator><general>American Chemical Society</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>7QO</scope><scope>7ST</scope><scope>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>SOI</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3892-8993</orcidid></search><sort><creationdate>20190102</creationdate><title>Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish</title><author>Brown, A. Ross ; Green, Jon M ; Moreman, John ; Gunnarsson, Lina M ; Mourabit, Sulayman ; Ball, Jonathan ; Winter, Matthew J ; Trznadel, Maciej ; Correia, Ana ; Hacker, Christian ; Perry, Alexis ; Wood, Mark E ; Hetheridge, Malcolm J ; Currie, Richard A ; Tyler, Charles R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a490t-20b0474fb7b2d708e5850fabd6b4e88283c605362988a87bee481319577feafe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Aortic valve</topic><topic>Benzhydryl Compounds</topic><topic>Biomarkers</topic><topic>Bisphenol A</topic><topic>Blood flow</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular system</topic><topic>Chemicals</topic><topic>Child</topic><topic>Children</topic><topic>Collagen</topic><topic>Computer simulation</topic><topic>Curvature</topic><topic>Danio rerio</topic><topic>Embryos</topic><topic>Environmental science</topic><topic>Estrogens</topic><topic>Exposure</topic><topic>Extracellular matrix</topic><topic>Fetuses</topic><topic>Fluorescence</topic><topic>Heart</topic><topic>heart valve diseases</topic><topic>Heart valves</topic><topic>Histopathology</topic><topic>Humans</topic><topic>Metabolites</topic><topic>Molecular modelling</topic><topic>Organic chemistry</topic><topic>Phenols</topic><topic>Rheumatic heart disease</topic><topic>Structural integrity</topic><topic>tissues</topic><topic>transcriptomics</topic><topic>Ventricle</topic><topic>Wildlife</topic><topic>Xenoestrogens</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, A. Ross</creatorcontrib><creatorcontrib>Green, Jon M</creatorcontrib><creatorcontrib>Moreman, John</creatorcontrib><creatorcontrib>Gunnarsson, Lina M</creatorcontrib><creatorcontrib>Mourabit, Sulayman</creatorcontrib><creatorcontrib>Ball, Jonathan</creatorcontrib><creatorcontrib>Winter, Matthew J</creatorcontrib><creatorcontrib>Trznadel, Maciej</creatorcontrib><creatorcontrib>Correia, Ana</creatorcontrib><creatorcontrib>Hacker, Christian</creatorcontrib><creatorcontrib>Perry, Alexis</creatorcontrib><creatorcontrib>Wood, Mark E</creatorcontrib><creatorcontrib>Hetheridge, Malcolm J</creatorcontrib><creatorcontrib>Currie, Richard A</creatorcontrib><creatorcontrib>Tyler, Charles R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Environmental science & technology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, A. Ross</au><au>Green, Jon M</au><au>Moreman, John</au><au>Gunnarsson, Lina M</au><au>Mourabit, Sulayman</au><au>Ball, Jonathan</au><au>Winter, Matthew J</au><au>Trznadel, Maciej</au><au>Correia, Ana</au><au>Hacker, Christian</au><au>Perry, Alexis</au><au>Wood, Mark E</au><au>Hetheridge, Malcolm J</au><au>Currie, Richard A</au><au>Tyler, Charles R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish</atitle><jtitle>Environmental science & technology</jtitle><addtitle>Environ. Sci. Technol</addtitle><date>2019-01-02</date><risdate>2019</risdate><volume>53</volume><issue>1</issue><spage>463</spage><epage>474</epage><pages>463-474</pages><issn>0013-936X</issn><issn>1520-5851</issn><eissn>1520-5851</eissn><abstract>The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular-cardiovascular disease states.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>30520632</pmid><doi>10.1021/acs.est.8b04281</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3892-8993</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0013-936X |
| ispartof | Environmental science & technology, 2019-01, Vol.53 (1), p.463-474 |
| issn | 0013-936X 1520-5851 1520-5851 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6333396 |
| source | American Chemical Society; MEDLINE |
| subjects | Animal models Animals Aortic valve Benzhydryl Compounds Biomarkers Bisphenol A Blood flow Cardiovascular disease Cardiovascular diseases Cardiovascular system Chemicals Child Children Collagen Computer simulation Curvature Danio rerio Embryos Environmental science Estrogens Exposure Extracellular matrix Fetuses Fluorescence Heart heart valve diseases Heart valves Histopathology Humans Metabolites Molecular modelling Organic chemistry Phenols Rheumatic heart disease Structural integrity tissues transcriptomics Ventricle Wildlife Xenoestrogens Zebrafish |
| title | Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T21%3A19%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cardiovascular%20Effects%20and%20Molecular%20Mechanisms%20of%20Bisphenol%20A%20and%20Its%20Metabolite%20MBP%20in%20Zebrafish&rft.jtitle=Environmental%20science%20&%20technology&rft.au=Brown,%20A.%20Ross&rft.date=2019-01-02&rft.volume=53&rft.issue=1&rft.spage=463&rft.epage=474&rft.pages=463-474&rft.issn=0013-936X&rft.eissn=1520-5851&rft_id=info:doi/10.1021/acs.est.8b04281&rft_dat=%3Cproquest_pubme%3E2189550795%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2168881260&rft_id=info:pmid/30520632&rfr_iscdi=true |