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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\u2009=\u200962). 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 \u223c50%\u2013100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of \u223c1.3\u20132.8 (95% confidence limits from 1.2\u20133.1) ng\/ml compared to \u22640.5\u2009ng\/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\u20133.4) and 3.6 (95% CI: 2.2\u20133.1) ng\/ml, respectively, compared to &amp;lt;1\u2009ng\/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.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab028","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T17:45:41Z","timestamp":1614275141000},"page":"215-228","source":"Crossref","is-referenced-by-count":49,"title":["Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation"],"prefix":"10.1093","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-7083","authenticated-orcid":false,"given":"Julia R","family":"Varshavsky","sequence":"first","affiliation":[{"name":"Program on Reproductive Health and the Environment, University of California, San Francisco (UCSF), San Francisco, California 94158"},{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-4535","authenticated-orcid":false,"given":"Joshua F","family":"Robinson","sequence":"additional","affiliation":[{"name":"Program on Reproductive Health and the Environment, University of California, San Francisco (UCSF), San Francisco, California 94158"},{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenisha A","family":"Puckett","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Kwan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirirak","family":"Buarpung","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayyan","family":"Aburajab","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L","family":"Gaw","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saunak","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songmei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Crispo","family":"Smith","sequence":"additional","affiliation":[{"name":"Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, California 94710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June-Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, California 94710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Zakharevich","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy R","family":"Gerona","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J","family":"Fisher","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences and Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, California 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey J","family":"Woodruff","sequence":"additional","affiliation":[{"name":"Program on Reproductive Health and the Environment, University of California, San Francisco (UCSF), San Francisco, California 94158"},{"name":"Center for Reproductive Sciences and 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