scholarly journals eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype

2012 ◽  
Vol 303 (1) ◽  
pp. R86-R93 ◽  
Author(s):  
Laura C. Kusinski ◽  
Joanna L. Stanley ◽  
Mark R. Dilworth ◽  
Cassandra J. Hirt ◽  
Irene J. Andersson ◽  
...  

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 14C-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent 14C-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.

2018 ◽  
pp. 184-195
Author(s):  
Minh Son Pham ◽  
Vu Quoc Huy Nguyen ◽  
Dinh Vinh Tran

Small for gestational age (SGA) and fetal growth restriction (FGR) is difficult to define exactly. In this pregnancy condition, the fetus does not reach its biological growth potential as a consequence of impaired placental function, which may be because of a variety of factors. Fetuses with FGR are at risk for perinatal morbidity and mortality, and poor long-term health outcomes, such as impaired neurological and cognitive development, and cardiovascular and endocrine diseases in adulthood. At present no gold standard for the diagnosis of SGA/FGR exists. The first aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines. Another aim to summary a number of interventions which are being developed or coming through to clinical trial in an attempt to improve fetal growth in placental insufficiency. Key words: fetal growth restriction (FGR), Small for gestational age (SGA)


2009 ◽  
Vol 20 (4) ◽  
pp. 269-281 ◽  
Author(s):  
EDUARD GRATACÓS ◽  
ELISENDA EIXARCH ◽  
FATIMA CRISPI

Selective fetal growth restriction (sFGR) has been reported to occur in about 10–15% of monochorionic (MC) twins. The diagnosis of sFGR has been based on variable criteria including estimated fetal weight (EFW), abdominal circumference and/or the degree of fetal weight discordance. Recent studies tend to use a simple definition which includes the presence of an EFW less than the 10th percentile in the smaller twin. Some would argue that the intertwin fetal weight discordance should be included in the definition. Indeed this factor plays a major role in the complications presented by these cases. While the majority of cases with one fetus below the 10th percentile usually will also present with a large intertwin EFW discordance, the contrary is not always true. Thus, it is possible to find MC twins with remarkable intertwin EFW discordance but the EFW of both fetuses are still within normal ranges. Although it appears to be common sense that a large intertwin discrepancy might represent a higher risk for some of the complications described later in this review, there is no consistent evidence to support this notion. Therefore, due to its simplicity, a definition based on an EFW below 10th percentile in one twin is probably the most useful for clinical and research purposes.


2006 ◽  
Vol 165 (10) ◽  
pp. 717-725 ◽  
Author(s):  
Nicole Mamelle ◽  
Magali Boniol ◽  
Olivier Rivière ◽  
Marie O. Joly ◽  
Georges Mellier ◽  
...  

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 180-193 ◽  
Author(s):  
Erica D. Watson ◽  
James C. Cross

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.


Neonatology ◽  
2001 ◽  
Vol 80 (4) ◽  
pp. 277-285 ◽  
Author(s):  
N. Mamelle ◽  
V. Cochet ◽  
O. Claris

2022 ◽  
Vol 226 (1) ◽  
pp. S165
Author(s):  
James D. Toppin ◽  
Miranda Long ◽  
Rick Tivis ◽  
Joseph Biggio ◽  
Frank Williams

2022 ◽  
Vol 226 (1) ◽  
pp. S179
Author(s):  
Miranda Long ◽  
Angela Nakahara ◽  
Ardem Elmayan ◽  
Rick Tivis ◽  
Joseph Biggio ◽  
...  

2021 ◽  
Vol 20 (5) ◽  
pp. 76-86
Author(s):  
N.M. Podzolkova ◽  
◽  
Yu.V. Denisova ◽  
M.Yu. Skvortsova ◽  
T.V. Denisova ◽  
...  

Fetal growth restriction (FGR) refers to pregnancy complications associated with an increased risk of perinatal morbidity and mortality and is defined in the Russian-language literature as the fetal size and weight retardation in relation to the norm for a given gestational age, and in the English-language literature – as the inability of the fetus to realize its genetically determined growth potential. FGR is the cause of 43% of stillbirths of unspecified etiology, and some cases remain undiagnosed even in high-risk populations due to the lack of universal diagnostic standards for this pathology. The review presents a critical analysis of the existing definitions of FGR, the latest data on risk factors, an assessment of diagnostic methods for its early and late forms, the prospects of using biomarkers and instrumental methods of examination in predicting adverse perinatal outcomes, and an algorithm for the management of pregnancy complicated by FGR. For a more complete coverage of the literature and deeper understanding of the nosology, attention is focused on FGR that is not accompanied by preeclampsia and other hypertensive disorders, which occur in about 30% of cases. Key words: placental insufficiency, fetometry, percentile, pulsatility index, fetal growth restriction For citation: Podzolkova N.M., Denisova Yu.V., Skvortsova M.Yu., Denisova T.V., Shovgenova D.S. Fetal growth restriction: unresolved issues of risk stratification, early diagnosis, and obstetric management. Vopr. ginekol. akus. perinatol. (Gynecology, Obstetrics and Perinatology). 2021; 20(5): 76–86. (In Russian). DOI: 10.20953/1726-1678-2021-5-76-86


2020 ◽  
Vol 222 (1) ◽  
pp. S606-S607
Author(s):  
Sara Jones ◽  
Amir Aviram ◽  
Ludmila Porto ◽  
Tianhua Huang ◽  
Jon Barrett ◽  
...  

2020 ◽  
Vol 42 (5) ◽  
pp. 677
Author(s):  
Sara Jones ◽  
Amir Aviram ◽  
Ludmila Porto ◽  
Tianhua Huang ◽  
Jon Barrett ◽  
...  

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