{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:21:38Z","timestamp":1788916898190,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5 K12 HD057022\u201007"],"award-info":[{"award-number":["5 K12 HD057022\u201007"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["7PRE33410652"],"award-info":[{"award-number":["7PRE33410652"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["ROI HL138181"],"award-info":[{"award-number":["ROI HL138181"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HD088590"],"award-info":[{"award-number":["R01 HD088590"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The hypoxia of high\u2010altitude (HA) residence increases the risk of intrauterine growth restriction (IUGR) and preeclampsia 3\u2010fold, augmenting perinatal morbidity and mortality and the risk for childhood and adult disease. Currently, no effective therapies exist to prevent these vascular disorders of pregnancy. The peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u2010\u03b3) is an important regulator of uteroplacental vascular development and function and has been implicated in the pathogenesis of IUGR and preeclampsia. Here, we used a model of HA pregnancy in mice to determine whether hypoxia\u2010induced fetal growth restriction reduces placental PPAR\u2010\u03b3 protein expression and placental vascularization and, if so, to evaluate the effectiveness of the selective PPAR\u2010\u03b3 agonist pioglitazone (PIO) for preventing hypoxia\u2010induced IUGR. Hypoxia resulted in asymmetric IUGR, placental insufficiency, and reduced placental PPAR\u2010\u03b3 expression; PIO prevented approximately half of the fetal growth restriction and attenuated placental insufficiency. PIO did not affect fetal growth under normoxia. Although PIO was beneficial for fetal growth, PIO treatment reduced placental vascular density of the labrynthine zone in normoxic and hypoxic (Hx) conditions, and mean vascular area was reduced in the Hx group. Our results suggest that pharmacological PPAR\u2010\u03b3 activation is a potential strategy for preventing IUGR in pregnancies complicated by hypoxia, although further studies are needed to identify its likely metabolic or vascular mechanisms.\u2014Lane, S. L., Dodson, R. B., Doyle, A. S., Park, H., Rathi, H., Matarrazo, C. J., Moore, L. G., Lorca, R. A., Wolf son, G. H. Julian, C. G. Pharmacological activation of peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u2010\u03b3) protects against hypoxia\u2010associated fetal growth restriction. FASEB J. 33, 8999\u20139007 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900214r","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T17:54:43Z","timestamp":1556646883000},"page":"8999-9007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Pharmacological activation of peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u2010\u03b3) protects against hypoxia\u2010associated fetal growth restriction"],"prefix":"10.1096","volume":"33","author":[{"given":"Sydney L.","family":"Lane","sequence":"first","affiliation":[{"name":"Integrated Physiology Program University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Blair Dodson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrea S.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and University of Colorado Denver  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haemin","family":"Park","sequence":"additional","affiliation":[{"name":"Colorado Undergraduate Research in Environmental Health Sciences University of Colorado Denver  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinal","family":"Rathi","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and University of Colorado Denver  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Matarrazo","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna G.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n A.","family":"Lorca","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel H.","family":"Wolfson","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen G.","family":"Julian","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.384"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025388901248"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(98)70439-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(87)90133-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.04.032"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.87.6.1003"},{"key":"e_1_2_8_8_1","first-page":"617","article-title":"Pathophysiology of fetal growth restriction: implications for diagnosis and surveillance","volume":"59","author":"Baschat A. 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