Prenatal AD.VEGF gene therapy increases fetal growth velocity and alters uterine artery vascular reactivity in the absence of a measurable effect on uterine blood flow in a sheep model of fetal growth restriction

2012 ◽  
Vol 97 (Suppl 1) ◽  
pp. A1.1-A1 ◽  
Author(s):  
DJ Carr ◽  
RP Aitken ◽  
JS Milne ◽  
V Mehta ◽  
DM Peebles ◽  
...  
2019 ◽  
Vol 83 ◽  
pp. 63-72 ◽  
Author(s):  
Colette N. Miller ◽  
Urmila P. Kodavanti ◽  
Erica J. Stewart ◽  
Mette Schaldweiler ◽  
Judy H. Richards ◽  
...  

2017 ◽  
Vol 8 (5) ◽  
pp. 550-555 ◽  
Author(s):  
H. Dickinson ◽  
S. Ellery ◽  
M. Davies-Tuck ◽  
M. Tolcos ◽  
I. Nitsos ◽  
...  

Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38–39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongna Yu ◽  
Meiqin Yuan ◽  
Ling Wang ◽  
Xia Li ◽  
Meiping Jiang

Objective. To explore the correlation between parturients’ uterine artery blood flow spectra in the first and second trimesters of pregnancy and fetal growth restriction (FGR). Methods. The data of parturients treated in our hospital from February 2018 to February 2020 were retrospectively analyzed, 50 parturients with FGR were selected as the FGR group, and other 50 healthy cases were selected as the control group. In the first trimester (11-12 weeks of gestation) and the second trimester of pregnancy (13–24 weeks of gestation), the parturients of the two groups accepted the color Doppler ultrasonography (CDS), their hemodynamics indicators of uterine artery were recorded, and the correlation between their uterine artery blood flow spectra in the two periods and FGR was analyzed with the Receiver Operating Characteristic (ROC) curve. Results. No statistical differences in the parturients’ general information including age, gestational weeks, gravidity, and parity between the two groups were observed ( P  > 0.05); the newborn’s body weight, Apgar scores, number of preterm infants, and the number of infants transferring to the neonatal intensive care unit (NICU) were significantly different between the two groups ( P  < 0.05); in the first and second trimesters of pregnancy, the uterine artery pulsatility index (UtA-PI), uterine artery resistance index (UtA-RI), maximal systolic flow velocity, and systolic/diastolic (UtA-S/D) ratio were significantly higher in the FGR group than in the control group ( P  < 0.05), and the time-averaged maximal velocity (TAMX) was significantly lower in the FGR group than in the control group ( P  < 0.001); in early pregnancy, the incidence of early diastolic notch at bilateral uterine arteries between the two groups was not significantly different ( P  > 0.05), and the unilateral and total incidence in the first trimester as well as the unilateral, bilateral, and total incidence in the second trimester were significantly higher in the FGR group than in the control group ( P  < 0.05); in the first trimester, the sensitivity of detecting FGR with a uterine artery blood flow spectrum was 0.820, AUC (95% CI) = 0.840 (0.757–0.923), and in the second trimester, it was 0.860, AUC (95% CI) = 0.900 (0.832–0.968). Conclusion. There is a correlation between uterine artery blood flow spectra in the first and second trimesters of pregnancy and FGR, and the sensitivity of spectrum in the first trimester is higher than that in the second trimester, presenting a better clinical application value.


2019 ◽  
Vol 102 (3) ◽  
pp. 660-670 ◽  
Author(s):  
Sydney L Lane ◽  
Alexandrea S Doyle ◽  
Elise S Bales ◽  
Ramón A Lorca ◽  
Colleen G Julian ◽  
...  

Abstract Incomplete maternal vascular responses to pregnancy contribute to pregnancy complications including intrauterine growth restriction (IUGR) and preeclampsia. We aimed to characterize maternal vascular dysfunction in a murine model of fetal growth restriction as an approach toward identifying targetable pathways for improving pregnancy outcomes. We utilized a murine model of late-gestation hypoxia-induced IUGR that reduced E18.5 fetal weight by 34%. Contrary to our hypothesis, uterine artery blood flow as measured in vivo by Doppler ultrasound was increased in mice housed under hypobaric hypoxia (385 mmHg; 5500 m) vs normoxia (760 mmHg; 0 m). Using wire myography, uterine arteries isolated from hypoxic mice had similar vasodilator responses to the two activators A769662 and acetylcholine as those from normoxic mice, although the contribution of an increase in nitric oxide production to uterine artery vasodilation was reduced in the hypoxic vs normoxic groups. Vasoconstrictor responses to phenylephrine and potassium chloride were unaltered by hypoxia. The levels of activated adenosine monophosphate-activated protein kinase (AMPK) were reduced with hypoxia in both the uterine artery and placenta as measured by western blot and immunohistochemistry. We concluded that the rise in uterine artery blood flow may be compensatory to hypoxia but was not sufficient to prevent fetal growth restriction. Although AMPK signaling was reduced by hypoxia, AMPK was still receptive to pharmacologic activation in the uterine arteries in which it was a potent vasodilator. Thus, AMPK activation may represent a new therapy for pregnancy complications involving reduced uteroplacental perfusion.


2020 ◽  
Vol 598 (18) ◽  
pp. 4093-4105
Author(s):  
Sydney L. Lane ◽  
Julie A. Houck ◽  
Alexandrea S. Doyle ◽  
Elise S. Bales ◽  
Ramón A. Lorca ◽  
...  

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