Abstract 192: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Reprograms Fetal Predisposition to Obesity in Intra-uterine Growth Restriction
We have shown that intra placental adenoviral mediated gene transfer of (Ad hIGF1) corrects birth weight in a new surgical mouse IUGR model. Evidence shows that IUGR offspring are predisposed to increased risk of adult diseases. We hypothesized that intraplacental Ad hIGF1 not only restores birth weight in this IUGR model but prevents adult onset obesity through fetal reprogramming Laparotomy was done at day 18 on time pregnant C57BL/6J mice, divided into 3 groups. Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF1; n= 16. Pups were delivered on day 20, cross fostered to surrogate CD1 mice, sorted by gender at 4 weeks and followed up to 24 weeks. Body weight, fat pad weight, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA Compared to SHAM, IUGR significantly reduced birth weight, restored to normal in IUGR+IGF-1 (1.12± .1vs 0.9± .1 vs 1.09± .1 g, p= .001). At 8 weeks, IUGR achieved mean body weight equivalent to SHAM and IUGR+IGF-1. By week 21, regardless of sex, IUGR significantly increased weight (obesity) compared to sham and IUGR+IGF-1 (fig A). Total fad pad weights were significantly higher in IUGR compared to SHAM but were restored to normal in IUGR+IGF1 (fig B). IUGR significantly increased fasting serum leptin, compared to Sham and restored to normal in IUGR+IGF1 ( .6± .4vs 5.7± 1.1 vs .8± .4 pg/ug, p= .01). No difference in food consumption amongst the groups Intra placental gene transfer of Ad hIGF1 corrects birth weight in IUGR mice model and attenuates the risk of postnatal obesity, This support the concept that in utero reprogramming of fetal predisposition to obesity is a novel approch to treatment of IUGR.
- © 2012 by American Heart Association, Inc.