期刊
HUMAN GENE THERAPY
卷 27, 期 12, 页码 997-1007出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2016.046
关键词
maternal gene therapy; fetal growth restriction; adenovirus VEGF; guinea pig; placental insufficiency
资金
- Action Medical Research [SP4409]
- UCL/UCLH NIHR Comprehensive Biomedical Research Centre
- Rosetrees Trust and Magnus Life Science
- British Heart Foundation
- Ark Therapeutics Oy, Kuopio, Finland
- Action Medical Research [1738] Funding Source: researchfish
- British Heart Foundation [RG/11/11/29050] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10046] Funding Source: researchfish
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 periconceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A(165) or Ad.LacZ (1 x 10(10)vp) 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-A(165)-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/hematologicalexaminationwere comparable with controls. Uterine artery relaxation in Ad.VEGF-A(165)-treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A(165) increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据