VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Sheep to Enhance Fetal Growth

In this chapter, we describe a safe and effective approach to achieve local VEGF gene transfer to the uterine arteries in pregnant sheep using direct injection of viral vectors into the uterine arteries. This approach resulted in improved fetal growth in growth-restricted pregnancies. Adenoviral vectors encoding VEGF-A165 or a reporter gene β-galactosidase were dissolved in 10 mL normal saline shortly before administration. A midline laparotomy was performed and the course of the uterine artery identified. The main trunk (just prior to the first bifurcation) was mobilized by dissection and a vessel loop placed beneath it in order to elevate the artery, which was then occluded digitally just proximal to the planned injection site. The adenoviral solution was slowly injected over 1 min, and the occlusion was maintained for a further 4 min to maximize transduction of the downstream endothelium. After ensuring hemostasis, the abdomen was closed in layers.