73 Evaluating the influence of maternal obesity on perinatal neuroinflammation

Intrauterine infection and inflammation are known risk factors for a spectrum of adverse neurodevelopment outcomes. While obese women are at higher risk of infection it remains unknown if obesity itself is an independent risk factor for adverse neurodevelopmental sequela. We aimed to examine the influence of maternal obesity on fetal brain development utilizing a murine model of preterm birth and perinatal brain injury. Obese dams were generated and maintained through pregnancy on a high-fat diet. All dams were paired with males on normal diet. Dams were randomized to receive an intrauterine injection of bacterial endotoxin (LPS) or vehicle (PBS) as a control on embryo day 15.5. Fetal brains were harvested 6hrs following injections, prior to preterm delivery and analyzed for the expression of proinflammatory cytokines (Il1b, Il6, and Tnf) and an immune related panel of genes. Aside from maternal weights, there was no difference in pregnancy characteristics (Table 1). There was a two-fold increase in the expression of Il1b, Il6, and Tnf in fetal brains from obese vs. non-obese dams that received LPS (Figure1A: p<0.05). In PBS controls there was no difference in gene expression for these inflammatory cytokines. Analysis with an immune response panel containing 92 inflammation related genes revealed seven that were differentially expressed with obesity and LPS exposure (Figure1B). Upregulated genes in fetal brains from obese dams were Cxcl11 and Cyp1a2. Downregulated were Ccr7, Lif, Cd8a, Cd19, and Lta. The neuroinflammatory response to LPS was greater in embryos from obese dams. Though key inflammatory genes related to innate immunity were elevated (Il1b, Il6, Tnf), those linked to adaptive immunity (Cd8a, Cd19, Ccr7) and neurodevelopment (Lif) were downregulated. Obesity alone did not alter fetal brain inflammatory gene expression. Preterm inflammatory responses known to alter fetal neurodevelopment are altered with maternal obesity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)