46: Insulin growth factor 1 gene therapy restores altered umbilical artery (UA) doppler indices in a mouse model of growth restriction (IUGR)

Previous work in our laboratory demonstrated that intra-placental gene therapy with adenoviral insulin growth factor 1(AdIGF1) corrects fetal weight in a surgical mouse model of intrauterine growth restriction. Doppler indices have not been evaluated. Aim of this study is to investigate the effect of intraplacental IGF-1 over-expression on fetal/placental hemodynamics by assessing pre & post treatment UA Doppler indices in a surgical mouse model of IUGR Laparotomy was performed on pregnant C57 mice(n=24) at embryonic day 18 and pups were divided into 3 groups. Control: Sham operated; IUGR: ligation of a uterine artery branch; IUGR+IGF1: injection of Ad IGF1 after ligation. Pups were delivered by C-section at day 20. 2D and trans-uterine Doppler imaging was performed pre-ligation and prior to delivery. Data collected was: birth survival, UA peak systolic velocity(PSV), end diastolic velocity(EDV), Systolic/Diastolic(S/D) ratio, pulsatility index(PI) and resistance index(RI) and heart rate (HR). Data analysed using ANOVA Fetal survival in the IUGR group was 75%(18/24) vs. 96%(23/24) in the IUGR+IGF1 vs 100% in the Control. IUGR group demonstrated AEDV in 12%(3/24) and REDV 12%(3/24) of the cases vs. only one case of REDV (1/24) in IUGR+IGF1. As compared to Sham, IUGR demonstrated a significant reduction in EDV, PSV, HR with a significant increase PI, RI and S/D ratio (Table1). Interestingly, IGF-Treated normalized altered indices in PSV(66±4.3vs 56±4.5,p=0.02), EDV (6.2±0.3vs4.2±0.4,p=0.007) and HR(78±10vs45±12p= 0.0001) as compared to IUGR group. IGF-Treated restored S/D ratio as compared to IUGR. No differences were detected in other variables Intra-placental gene transfer of Ad-IGF1 restores altered umbilical artery Doppler indices in a surgical mouse model of growth restriction. Compensatory changes in UA Doppler indices after gene therapy open a new paradigm for assessing effective treatment and prevention in animal model of IUGR.