{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:46:32Z","timestamp":1791308792520,"version":"4.3.1"},"reference-count":43,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2012,7,1]]},"abstract":"<jats:p>Fetal growth restriction (FGR) is the inability of a fetus to reach its genetically predetermined growth potential. In the absence of a genetic anomaly or maternal undernutrition, FGR is attributable to \u201cplacental insufficiency\u201d: inappropriate maternal\/fetal blood flow, reduced nutrient transport or morphological abnormalities of the placenta (e.g., altered barrier thickness). It is not known whether these diverse factors act singly, or in combination, having additive effects that may lead to greater FGR severity. We suggest that multiplicity of such dysfunction might underlie the diverse FGR phenotypes seen in humans. Pregnant endothelial nitric oxide synthase knockout (eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>) dams exhibit dysregulated vascular adaptations to pregnancy, and eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>fetuses of such dams display FGR. We investigated the hypothesis that both altered vascular function and placental nutrient transport contribute to the FGR phenotype. eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>dams were hypertensive prior to and during pregnancy and at embryonic day (E) 18.5 were proteinuric. Isolated uterine artery constriction was significantly increased, and endothelium-dependent relaxation significantly reduced, compared with wild-type (WT) mice. eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>fetal weight and abdominal circumference were significantly reduced compared with WT. Unidirectional maternofetal<jats:sup>14<\/jats:sup>C-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent<jats:sup>14<\/jats:sup>C-MeAIB uptake into mouse placental vesicles were both significantly lower in eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>fetuses, indicating diminished placental nutrient transport. eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mouse placentas demonstrated increased hypoxia at E17.5, with elevated superoxide compared with WT. We propose that aberrant uterine artery reactivity in eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mice promotes placental hypoxia with free radical formation, reducing placental nutrient transport capacity and fetal growth. We further postulate that this mouse model demonstrates \u201cuteroplacental hypoxia,\u201d providing a new framework for understanding the etiology of FGR in human pregnancy.<\/jats:p>","DOI":"10.1152\/ajpregu.00600.2011","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T04:26:21Z","timestamp":1336019181000},"page":"R86-R93","source":"Crossref","is-referenced-by-count":100,"title":["eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype"],"prefix":"10.1152","volume":"303","author":[{"given":"Laura C.","family":"Kusinski","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre, School of Biomedicine, Manchester Academic Health Science Centre, The University of Manchester, St. Mary's Hospital, Manchester, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Stanley","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, University of Alberta, Alberta, Edmonton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Dilworth","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, School of Biomedicine, Manchester Academic Health Science Centre, The University of Manchester, St. Mary's Hospital, Manchester, United Kingdom; 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