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Perinatal and long term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth restricted guinea pig fetus

Vaughan, OR; Rossi, CA; Ginsberg, Y; White, A; Hristova, M; Sebire, NJ; Martin, J; ... David, AL; + view all (2018) Perinatal and long term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth restricted guinea pig fetus. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology , 315 (2) R344-R353. 10.1152/ajpregu.00210.2017. Green open access

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Abstract

Uterine artery application of adenoviral vascular endothelial growth factor gene therapy (Ad.VEGF-A165) increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1x1010 viral particles, n=15) or vehicle (n=10), delivered to the external surface of the uterine arteries, in mid-pregnancy. Ad libitum fed controls received vehicle only (n=14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR and FGR+Ad.VEGF-A165 animals. Compared to controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whilst both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups (P<0.05 ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring, irrespective of Ad.VEGF-A165 treatment, but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic nor mean arterial pressure, adrenal weight, basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure.

Type: Article
Title: Perinatal and long term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth restricted guinea pig fetus
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpregu.00210.2017
Publisher version: https://doi.org/10.1152/ajpregu.00210.2017
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: blood pressure, developmental programming, growth, placenta, vascular endothelial growth factor
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10050539
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