Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 303, Issue 1, Pages R86-R93Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00600.2011
Keywords
nitric oxide; pregnancy; placental insufficiency
Categories
Funding
- BBSRC
- MRC [92495]
- MRC [G0802770] Funding Source: UKRI
- Medical Research Council [G0802770] Funding Source: researchfish
Ask authors/readers for more resources
Kusinski LC, Stanley JL, Dilworth MR, Hirt CJ, Andersson IJ, Renshall LJ, Baker BC, Baker PN, Sibley CP, Wareing M, Glazier JD. eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype. Am J Physiol Regul Integr Comp Physiol 303: R86-R93, 2012. First published May 2, 2012; doi:10.1152/ajpregu.00600.2011.-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 placental insufficiency: 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(-/-)) dams exhibit dysregulated vascular adaptations to pregnancy, and eNOS(-/-) 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(-/-) 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(-/-) fetal weight and abdominal circumference were significantly reduced compared with WT. Unidirectional maternofetal C-14-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent C-14-MeAIB uptake into mouse placental vesicles were both significantly lower in eNOS(-/-) fetuses, indicating diminished placental nutrient transport. eNOS(-/-) mouse placentas demonstrated increased hypoxia at E17.5, with elevated superoxide compared with WT. We propose that aberrant uterine artery reactivity in eNOS(-/-) mice promotes placental hypoxia with free radical formation, reducing placental nutrient transport capacity and fetal growth. We further postulate that this mouse model demonstrates uteroplacental hypoxia, providing a new framework for understanding the etiology of FGR in human pregnancy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available