title: Maternal Therapy with Ad.VEGF-A165Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.
abstract: In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A165or Ad.LacZ (1 × 1010vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A165-treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A165-treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A165increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Anna M
authors.initials: AM
authors.lastname: Swanson
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Rossi
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Keren
authors.initials: K
authors.lastname: Ofir
authors.affiliation: 2 Centre for Cardiovascular Biology and Medicine , UCL, London, United Kingdom .
authors.forename: Vedanta
authors.initials: V
authors.lastname: Mehta
authors.affiliation: 3 Biological Services Unit, Royal Veterinary College, London, United Kingdom .
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.affiliation: 3 Biological Services Unit, Royal Veterinary College, London, United Kingdom .
authors.forename: Hannah
authors.initials: H
authors.lastname: Barker
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Agata
authors.initials: A
authors.lastname: Ledwozyw
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Owen
authors.initials: O
authors.lastname: Vaughan
authors.affiliation: 2 Centre for Cardiovascular Biology and Medicine , UCL, London, United Kingdom .
authors.forename: John
authors.initials: J
authors.lastname: Martin
authors.affiliation: 2 Centre for Cardiovascular Biology and Medicine , UCL, London, United Kingdom .
authors.forename: Ian
authors.initials: I
authors.lastname: Zachary
authors.affiliation: 4 Department of Paediatric Pathology, Institute of Child Health , UCL, London, United Kingdom .
authors.forename: Neil
authors.initials: N
authors.lastname: Sebire
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Donald M
authors.initials: DM
authors.lastname: Peebles
authors.affiliation: 1 Prenatal Cell and Gene Therapy Group, Institute for Women's Health , UCL, London, United Kingdom .
authors.forename: Anna L
authors.initials: AL
authors.lastname: David
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000628:therapy*; D020567:Fetal Weight / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D006168:Guinea Pigs; D011247:Pregnancy; D012039:Regional Blood Flow; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: adenovirus VEGF; fetal growth restriction; guinea pig; maternal gene therapy; placental insufficiency