Project Summary / Abstract Delivery via cesarean section (CS) now makes up roughly one third of all births in the United States. After CS delivery, newborns experience lower levels of several ‘birth signaling hormones’ such as oxytocin, vasopressin, and corticosteroids. Birth is a sensitive period for the signaling of these hormones, and so changes in their levels at birth can affect their regulation throughout development. Besides being involved in birth, these same hormones also regulate metabolism behavior in later life. We hypothesize this is why delivery by CS is associated with substantially higher rates of childhood obesity. We have begun to explore the connections between birth mode and subsequent metabolic regulation using the prairie vole (Microtus ochrogaster). The prairie vole is one of the few rodent models that allows us to examine the physiology underlying energy regulation without the burden of chronic cold stress brought on by conventional, room temperature housing. Our recent findings suggest that prairie voles delivered via CS experience changes in their thermoregulation, social behavior, and metabolic regulation sufficient to produce increased weight gain across development. In the present study, we will investigate this further to assess whether voles delivered by CS are at increased risk for visceral adiposity -one of the most dangerous aspects of obesity in humans. We will fully characterize subjects’ energy budgets as well as the brain functioning that underlies metabolism in terms of anatomy, connectivity and the regulation of the birth signaling hormones. Finally, we test whether replacing the missing hormone surge in CS newborns can avoid the metabolic outcomes typically seen in children and voles delivered by CS. In so doing, we hope to offer a simple, straightforward, and cost-effective strategy to reduce childhood obesity in this population. We hypothesize that a CS delivery represents delivery without the full complement of birth signaling hormones and as such will result differences in neuroendocrinology and metabolism throughout development.

PROJECT NARRATIVE The proposed research advances our understanding of how birth mode affects development. The same hormones that are involved in birth also regulate metabolism, and when we manipulate these hormones to help improve birth outcomes, we may be producing long-term changes in offspring metabolism and weight gain. The proposed work will help us understand how these common birth interventions may impact the development of the fetal brain and subsequent health.