Loading…
This program is subject to change. Speakers are added as confirmations are received.
Please  note that preconference courses require separate registration.
Downloads:   Oral Abstracts   Poster Abstracts
Back To Schedule
Monday, July 9 • 15:15 - 15:30
Session 1 | Fetal Therapy: 1-2 Neurodevelopmental effects of maternal uterine artery Ad.VEGF-A165 treatment for fetal growth restriction in fetal guinea pigs

Sign up or log in to save this to your schedule, view media, leave feedback and see who's attending!

Neurodevelopmental effects of maternal uterine artery Ad.VEGF-A165 treatment for fetal growth restriction in fetal guinea pigs
Tara Krishnan1, Mariya Hristova2, Owen Vaughan1, Carlo Rossi1, Jan Nouza2, Anna David3

1Institute for Women's Health, University College London, London, United Kingdom
2Institute for Women's Health, University College London, United Kingdom, London, United Kingdom
3Institute for Women's Health, University College London,, London, , United Kingdom
Objectives
Fetal growth restriction(FGR) is the failure of a fetus to achieve normal intrauterine growth. There is currently no treatment available for FGR, which can cause behavioural disorders, impaired motor function, and carries a high mortality rate. FGR fetuses have reduced brain size, altered brain-to-bodyweight ratio and increased inflammation and neural cell death when compared with normally grown fetuses. Previously we showed that maternal uterine artery administration of an adenovirus vector containing the VEGF-A165 isoform(Ad.VEGF-A165) to pregnant guinea pigs with FGR mid-gestation increases fetal weight at term. Here we studied the effects of treatment on neurodevelopment in FGR guinea pig fetuses.
Methods
To induce FGR, Dunkin Hartley guinea pigs were fed normally (control, n=7) or 70% calorie intake one month before conception and during pregnancy. FGR dams received Ad.VEGF-A165 (n=9, FGR+VEGF group) or a vehicle (pluronic gel, n=7, FGR group) externally to their uterine arteries via laparotomy on day ~30 of pregnancy (term=65=days). Control dams underwent sham laparotomy. Fetal body and brain weights were determined on day~65, at post-mortem. Brain samples were fixed and sectioned (40 mm). Regional brain volumes, microglial ramification, astrogliosis and apoptosis were analysed using cresyl violet, IBA-1, GFAP and TUNEL stained sections respectively. Groups were compared using one-way ANOVA.
Results
Brain weight was reduced in FGR fetuses (2.268g±0.064g) but was similar to control values (2.531g±0.093g) in the FGR+VEGF group fetuses (2.517g±0.063g,P=0.02). There was no significant difference in fetal weight between the three groups (P>0.05). Consequently, brain:body weight ratio was lower in the FGR group (2.693g±0.082g), compared to the FGR+VEGF group fetuses (3.040g±0.081g) that were no different to controls (2.976g±0.120g,P=0.017). Microglial ramification was increased in cortex, hippocampus, thalamus, and striatum in FGR fetuses compared with control and FGR+VEGF fetuses. Astrogliosis was increased in FGR+VEGF fetuses in all analysed brain regions when compared with control fetuses. TUNEL staining showed no difference in apoptosis across the groups.
Conclusions
Administration of maternal uterine artery Ad.VEGF-A165 gene-therapy to FGR guinea pig pregnancies in mid-gestation improves fetal brain growth, normalises microglial activation, and does not adversely affect neurological anatomy or apoptosis. These data support the safety profile of maternal uterine artery Ad.VEGF therapy for the treatment of FGR.
This research was funded by Action Medical Research.

Moderators
avatar for Anna David

Anna David

Director, Elizabeth Garrett Anderson Institute for Women's Health at University College London
Anna David is Director of the Elizabeth Garrett Anderson Institute for Women’s Health at University College London in London. She is also Professor and Honorary Consultant in Obstetrics and Maternal Fetal Medicine at UCL Hospital. Her clinical practice specializes in fetal medicine... Read More →
avatar for Roland Devlieger

Roland Devlieger

Professor, University Hospitals Leuven

Speakers
avatar for Tara Krishnan

Tara Krishnan

Institute for Women's Health, University College London


Monday July 9, 2018 15:15 - 15:30 CEST
Okapi Room 2&3