Oxytocin and Vasopressin at Birth Prevent Hypoactivity and Excess Weight Gain in Vole Offspring Delivered by Cesarean Section

Abstract

Birth occurs during a sensitive period in brain development wherein hormones facilitate the dramatic shift in physiology that accomplishes the transition to extrauterine homeostasis. The surge in birth signaling hormones is abridged in cases of delivery by cesarean section (CS), which accounts for 32% of all births in the U.S. Epidemiological studies have associated birth via CS with increased risk of obesity in later life. Here, we sought to investigate this association using an experimental preclinical animal model, the prairie vole. Subjects were delivered either via vaginal delivery (VD) or CS and then cross-fostered. CS delivery led to increased body weight across development, which could be prevented with hormone rescue of oxytocin (OXT) and arginine vasopressin (AVP), delivered to neonates immediately after CS. This weight gain could not be attributed to differences in birth weight, parenting, food consumption, or thermoregulation; however, CS subjects moved slower than VD subjects, which hormone rescue reversed. Hormone rescue also reduced adiposity in adulthood among CS subjects. The dopamine system was dysregulated in the caudate/putamen of CS offspring, suggesting a neural mechanism for the decreased locomotion. Hormone rescue of CS neonates restored dopamine synthesis in the caudate/putamen and increased spontaneous locomotor activity. These findings suggest CS can lead to increased weight gain in part through a reduction of locomotion driven by long-lasting changes in striatal dopamine regulation, all of which can be prevented by treating CS neonates with a single peripheral administration of two birth-signaling hormones, OXT and AVP.