Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation
Abstract Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect...
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| Veröffentlicht in: | Toxicological sciences 2021-05, Vol.181 (2), p.215-228 |
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| creator | Varshavsky, Julia R Robinson, Joshua F Zhou, Yan Puckett, Kenisha A Kwan, Elaine Buarpung, Sirirak Aburajab, Rayyan Gaw, Stephanie L Sen, Saunak Gao, Songmei Smith, Sabrina Crispo Park, June-Soo Zakharevich, Igor Gerona, Roy R Fisher, Susan J Woodruff, Tracey J |
| description | Abstract
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%–100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3–2.8 (95% confidence limits from 1.2–3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5–3.4) and 3.6 (95% CI: 2.2–3.1) ng/ml, respectively, compared to |
| doi_str_mv | 10.1093/toxsci/kfab028 |
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Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%–100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3–2.8 (95% confidence limits from 1.2–3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5–3.4) and 3.6 (95% CI: 2.2–3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfab028</identifier><identifier>PMID: 33677611</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Biomarkers ; Environmental Toxicology ; Female ; Flame Retardants - toxicity ; Humans ; Organophosphates - toxicity ; Placenta ; Placentation ; Pregnancy</subject><ispartof>Toxicological sciences, 2021-05, Vol.181 (2), p.215-228</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-f92b75f64989e297e2441134489c0446e39795e168b8fe5797dc26f9593be92f3</citedby><cites>FETCH-LOGICAL-c490t-f92b75f64989e297e2441134489c0446e39795e168b8fe5797dc26f9593be92f3</cites><orcidid>0000-0001-6891-7083 ; 0000-0002-2421-4535</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33677611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Varshavsky, Julia R</creatorcontrib><creatorcontrib>Robinson, Joshua F</creatorcontrib><creatorcontrib>Zhou, Yan</creatorcontrib><creatorcontrib>Puckett, Kenisha A</creatorcontrib><creatorcontrib>Kwan, Elaine</creatorcontrib><creatorcontrib>Buarpung, Sirirak</creatorcontrib><creatorcontrib>Aburajab, Rayyan</creatorcontrib><creatorcontrib>Gaw, Stephanie L</creatorcontrib><creatorcontrib>Sen, Saunak</creatorcontrib><creatorcontrib>Gao, Songmei</creatorcontrib><creatorcontrib>Smith, Sabrina Crispo</creatorcontrib><creatorcontrib>Park, June-Soo</creatorcontrib><creatorcontrib>Zakharevich, Igor</creatorcontrib><creatorcontrib>Gerona, Roy R</creatorcontrib><creatorcontrib>Fisher, Susan J</creatorcontrib><creatorcontrib>Woodruff, Tracey J</creatorcontrib><title>Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Abstract
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%–100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3–2.8 (95% confidence limits from 1.2–3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5–3.4) and 3.6 (95% CI: 2.2–3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.</description><subject>Biomarkers</subject><subject>Environmental Toxicology</subject><subject>Female</subject><subject>Flame Retardants - toxicity</subject><subject>Humans</subject><subject>Organophosphates - toxicity</subject><subject>Placenta</subject><subject>Placentation</subject><subject>Pregnancy</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1LxDAQhoMofl89Sq6C1aTppp2LoLt-gaKInkvaTrbRtilJd9F_4M82uqvoyVMmed95JsNLyB5nR5yBOB7sqy_N8YtWBYuzFbIZXmXEIIbVZS1ZxjbIlvfPjHEuGayTDSFkmkrON8n7nZuqzva19X2tBqQXjWqRPuCgXKW6wR_SKzOtm7cgzKwzXfBUdFxja0rVBFV1FT0ztlXuBZ2nVtP7RpXYDaqhE5xjY_s23L58E-NReaSTWQBN6a2pokv0gxqM7XbImg5A3F2e2-Tp4vxxfBXd3F1ej09vojIBNkQa4iIdaZlABhhDinGScC6SJIOSJYlEASmMkMusyDSOUkirMpYaRiAKhFiLbXKy4PazosXq86dONXnvTFjhLbfK5H-VztT51M7zjEvBBATA0QJQOuu9Q_3Ty1n-mUm-yCRfZhIa9n9P_LF_hxAMBwuDnfX_wT4ASpebtg</recordid><startdate>20210527</startdate><enddate>20210527</enddate><creator>Varshavsky, Julia R</creator><creator>Robinson, Joshua F</creator><creator>Zhou, Yan</creator><creator>Puckett, Kenisha A</creator><creator>Kwan, Elaine</creator><creator>Buarpung, Sirirak</creator><creator>Aburajab, Rayyan</creator><creator>Gaw, Stephanie L</creator><creator>Sen, Saunak</creator><creator>Gao, Songmei</creator><creator>Smith, Sabrina Crispo</creator><creator>Park, June-Soo</creator><creator>Zakharevich, Igor</creator><creator>Gerona, Roy R</creator><creator>Fisher, Susan J</creator><creator>Woodruff, Tracey J</creator><general>Oxford University Press</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>5PM</scope><orcidid>https://orcid.org/0000-0001-6891-7083</orcidid><orcidid>https://orcid.org/0000-0002-2421-4535</orcidid></search><sort><creationdate>20210527</creationdate><title>Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation</title><author>Varshavsky, Julia R ; Robinson, Joshua F ; Zhou, Yan ; Puckett, Kenisha A ; Kwan, Elaine ; Buarpung, Sirirak ; Aburajab, Rayyan ; Gaw, Stephanie L ; Sen, Saunak ; Gao, Songmei ; Smith, Sabrina Crispo ; Park, June-Soo ; Zakharevich, Igor ; Gerona, Roy R ; Fisher, Susan J ; Woodruff, Tracey J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-f92b75f64989e297e2441134489c0446e39795e168b8fe5797dc26f9593be92f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomarkers</topic><topic>Environmental Toxicology</topic><topic>Female</topic><topic>Flame Retardants - toxicity</topic><topic>Humans</topic><topic>Organophosphates - toxicity</topic><topic>Placenta</topic><topic>Placentation</topic><topic>Pregnancy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Varshavsky, Julia R</creatorcontrib><creatorcontrib>Robinson, Joshua F</creatorcontrib><creatorcontrib>Zhou, Yan</creatorcontrib><creatorcontrib>Puckett, Kenisha A</creatorcontrib><creatorcontrib>Kwan, Elaine</creatorcontrib><creatorcontrib>Buarpung, Sirirak</creatorcontrib><creatorcontrib>Aburajab, Rayyan</creatorcontrib><creatorcontrib>Gaw, Stephanie L</creatorcontrib><creatorcontrib>Sen, Saunak</creatorcontrib><creatorcontrib>Gao, Songmei</creatorcontrib><creatorcontrib>Smith, Sabrina Crispo</creatorcontrib><creatorcontrib>Park, June-Soo</creatorcontrib><creatorcontrib>Zakharevich, Igor</creatorcontrib><creatorcontrib>Gerona, Roy R</creatorcontrib><creatorcontrib>Fisher, Susan J</creatorcontrib><creatorcontrib>Woodruff, Tracey J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Varshavsky, Julia R</au><au>Robinson, Joshua F</au><au>Zhou, Yan</au><au>Puckett, Kenisha A</au><au>Kwan, Elaine</au><au>Buarpung, Sirirak</au><au>Aburajab, Rayyan</au><au>Gaw, Stephanie L</au><au>Sen, Saunak</au><au>Gao, Songmei</au><au>Smith, Sabrina Crispo</au><au>Park, June-Soo</au><au>Zakharevich, Igor</au><au>Gerona, Roy R</au><au>Fisher, Susan J</au><au>Woodruff, Tracey J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2021-05-27</date><risdate>2021</risdate><volume>181</volume><issue>2</issue><spage>215</spage><epage>228</epage><pages>215-228</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>Abstract
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%–100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3–2.8 (95% confidence limits from 1.2–3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5–3.4) and 3.6 (95% CI: 2.2–3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>33677611</pmid><doi>10.1093/toxsci/kfab028</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-6891-7083</orcidid><orcidid>https://orcid.org/0000-0002-2421-4535</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Biomarkers Environmental Toxicology Female Flame Retardants - toxicity Humans Organophosphates - toxicity Placenta Placentation Pregnancy |
| title | Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation |
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