183: Maternal obesity and evidence of fetal programming of lipid metabolism

programming of lipid metabolism Beth Plunkett, Gina Morgan, Richard Silver, Susan Crawford NorthShore University HealthSystem, Department of Obstetrics and Gynecology, Evanston, IL, NorthShore University HealthSystem, Surgery, Evanston, IL OBJECTIVE: To determine if pregestational maternal obesity alters fetal lipid metabolism in a leptin-deficient mouse model. STUDY DESIGN: Leptin-deficient mice (ob/ob) lack appetite control and become obese through overeating. Fetuses of LEAN ob/ob dams were compared to fetuses of OBESE ob/ob dams. LEAN ob/ob dams were treated with exogenous leptin after weaning to maintain normal body weight and fertility. The OBESE ob/ob dams were treated only with periconceptional leptin. Leptin treatments were stopped in both groups after post-conception D6.5. Dams were mated to C57Bl6 wildtype (WT) studs and sacrificed on D18. Fetal livers were harvested and RNA extracted for Affymetrix gene array analysis and Ingenuity Pathway Assessment. RESULTS: Preconceptional weight was significantly lower in the LEAN (n 4) than OBESE (n 5; 20.7 2.9 vs. 28.5 2.3g, P 0.05) as was D18 glucose (196.0 36.9 vs. 172.3 41.2 mg/dL, respectively, P 0.05) and D18 insulin (1.00 0.5 and1.14 1.0 ng/ml, respectively, P 0.05). Fetal livers (n 3) demonstrated significant changes in the expressions of 15 genes related to lipid metabolism in the fetuses of LEAN versus OBESE. CONCLUSION: In a leptin-deficient mouse model, maternal preconceptional obesity independently changes expression of multiple genes involved in fetal lipid metabolism. The identified genes modulate physiological processes associated with glucose intolerance and triglyceride metabolism. These findings suggest that significant metabolic disturbance related to maternal obesity may begin in fetal life. 184 Neonatal neurologic evaluation in a retinoic acid induced rat myelomeningocele model Brendan Grubbs, Shelley Hough, Samer Assaf, Lisa Korst, Martin Pera, Ramen Chmait University of Southern California, Obstetrics & Gynecology, Los Angeles, CA, University of Southern California, Eli & Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA, USC Keck School of Medicine, Obstetrics & Gynecology, Los Angeles, CA, University of Melbourne, Florey Neuroscience Institute, and the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia OBJECTIVE: To evaluate the response to limb pinch in newborn rats with retinoic acid induced myelomeningocele. STUDY DESIGN: Pregnant (Day 10) Sprague-Dawley dams were gavage fed retinoic acid (60 mg/kg), as described by Danzer (Danzer E, et al. Experimental Neurology 2005; 194: 467-475), in order to generate open neural tube defects. Cesarean sections were performed on day 21.5, under isoflurane anesthesia, and forceps were used to lightly pinch a fore limb and a hind limb 3 times each. Withdrawal of the pinched limb each time, and full body squirm were considered positive reactions. To control for anesthesia and death prior to evaluation, only pups exhibiting a positive forelimb response were included in analysis. A 2-tailed Fisher’s exact test was used for analysis of the results. RESULTS: Of 44 rat fetuses exposed to retinoic acid, 40 (91%) developed a myelomeningocele. Ten of these pups were excluded for a negative forelimb pinch response. 26 of the 30 (86.7%) remaining pups with myelomeningoceles vs. 1 of 12 (8.3%) control pups exhibited a negative response to hind limb pinch, yielding an odds ratio of 71.5 (95% CI 6.1-1981.1, p 0.0001). CONCLUSION: Our findings verify the efficacy of the retinoic acid model, and demonstrate that rat pups affected by myelomeningocele were substantially more likely to exhibit a negative pinch response compared with control pups. Observation of the response to limb pinch in this model may be useful for evaluation following attempts at repair or regeneration of damaged neural tissue.