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We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4\u2009h) to either filtered air (FA) or O3 (0.3 or 1.0\u2009ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3\u2009ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaa164","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:12:48Z","timestamp":1603307568000},"page":"121-134","source":"Crossref","is-referenced-by-count":22,"title":["Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function"],"prefix":"10.1093","volume":"179","author":[{"given":"Marcus","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selita","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Herbert","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Begay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse L","family":"Denson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Zychowski","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ashley","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, New Mexico State University, Las Cruces, New Mexico 88003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Byrum","sequence":"additional","affiliation":[{"name":"Arkansas Children's Research Institute, Little Rock, Arkansas 72202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Mackintosh","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E","family":"Bleske","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K","family":"Ottens","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Campen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"2021092111024708700_kfaa164-B1","doi-asserted-by":"crossref","first-page":"E1968","DOI":"10.1073\/pnas.1616070114","article-title":"Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment","volume":"114","author":"Aragon","year":"2017","journal-title":"Proc. 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