Maternal obesity alters fetal neuroinflammation in a murine model of preterm birth

Abstract

BackgroundPreterm birth from intrauterine infection is a leading cause of neonatal neurologic morbidity. Maternal obesity is also associated with intra-amniotic infection and inflammation. It remains unknown if maternal obesity is a risk factor for fetal brain injury that occurs with premature birth. We hypothesize that maternal obesity intensifies fetal neuroinflammation within the setting of premature delivery. ObjectiveUtilizing a murine model, we aimed to examine the influence of maternal obesity on perinatal neuroinflammatory responses that arise with preterm birth. Study DesignObese dams were generated via a high-fat diet that was maintained through pregnancy. In parallel, non-obese (normal) dams received a control diet. All dams were paired with males on normal diet. Pregnant dams were randomized to receive an intrauterine injection of bacterial endotoxin (LPS) or the vehicle (PBS) on embryo day 15.5 of what it typically a 19-21 day gestation. Fetal brains were harvested 6 hours following injections and the expression of key inflammatory cytokines (Il1b, Il6, and Tnf) as well as panels of metabolic, immune, and inflammatory genes was analyzed. ResultsWith PBS there were no differences in gene expression related to maternal obesity. There were substantial differences in Il6 and immune/inflammatory expression profiles in fetal brains from obese versus normal dams that received LPS. Few differences were observed among the metabolic genes examined under these conditions. Gene expression patterns with maternal obesity associated with pathways related to white matter injury. ConclusionThe expression of neuroinflammatory markers instigated by bacterial endotoxin via intrauterine LPS, was greater in embryo brains obtained from obese dams. Expression profiles suggest that in combination with intrauterine inflammation, maternal obesity may increase the risk of fetal white matter injury. Further investigation is warranted towards understanding the relationship between maternal health and neurologic outcomes associated with prematurity.