Swanson, A;
Rossi, C;
Ofir, K;
Mehta, V;
Boyd, M;
Barker, H;
Ledwozyw, A;
... David, AL; + view all
(2016)
Maternal therapy with Ad.VEGF-A165 increases fetal weight at term in a guinea pig model of fetal growth restriction.
Human Gene Therapy
, 27
(12)
pp. 997-1007.
10.1089/hum.2016.046.
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Abstract
OBJECTIVES: We have demonstrated that transient uterine artery VEGF overexpression improves fetal growth in growth restricted sheep pregnancy. We tested this hypothesis in guinea pig pregnancies, where placental physiology more closely resembles that in humans. METHOD: Virgin guinea pigs were nutrient restricted peri-conceptually to create fetal growth restriction (FGR). At day 29-36 (term=65days) at laparotomy Ad.VEGF-A165 or Ad.LacZ (1x1010vp) were applied externally to the uterine circulation using a thermosensitive gel. Dams were sacrificed after 3-8 days or at term. Pups were weighed and tissues sampled for vector spread, VEGF expression and its downstream effects. RESULTS: Ad.VEGF-A165 significantly increased fetal weight at term (88.01±13.36g, n=26) compared to control Ad.LacZ treatment (85.52±13.00g, n=19, p=0.028). Brain, liver, lung weight and crown rump length were significantly larger 3-8 days post-administration, VEGF expression was demonstrated by ELISA and confirmed by immunohistochemistry in transduced tissues. RT-PCR of term samples confirmed vector transduction in target tissues, but the transgene was undetectable in fetal samples. Tissue histological analysis and blood biochemistry/haematological examination was normal. Uterine arteries from Ad.VEGF-A165-treated dams relaxed more completely than those from Ad.LacZ treated dams. CONCLUSIONS: Maternal uterine artery Ad.VEGF-A165 increases fetal growth velocity and term fetal weight in growth restricted guinea pig pregnancy.
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