GAPIBB · GLP1-R Agonists in Pregnancy- Impact on Baby's Brain

Obesity and associated metabolic diseases represent a significant health challenge and financial burden worldwide. Recently, a breakthrough has been made in the treatment of obesity with drugs such as semaglutide (Ozempic), which mimic endogenous glucagon-like peptide 1 (GLP1) action in the brain and cause weight loss via reduced food intake. The hypothalamus is the key brain region involved in the neuronal control of food intake. Recent research shows that perturbations to the maternal environment in pregnancy may interfere with early neural circuitry development in offspring and lead to life-long metabolic impairments that are a contributing factor of rising obesity rates. The increased Ozempic use in women of reproductive age has resulted in a rise in “Ozempic babies”, where women unexpectedly become pregnant whilst using Ozempic. However, there is limited data regarding Ozempic use in pregnant women to determine whether in utero exposure leads to adverse developmental effects in offspring. The offspring hypothalamus is potentially vulnerable to semaglutide exposure, due to it’s highly plastic developmental state and high GLP1R expression in both rodents and humans. This project is designed to test the hypothesis that in utero Ozempic exposure causes significant alterations to the development of hypothalamic feeding circuitry resulting in subsequent disruptions to metabolic control in the offspring. Using a rodent model of semaglutide administration to the mother in pregnancy, we will determine whether semaglutide exposure during fetal development affects hypothalamic circuitry and transcriptome at different ages from fetal through to adult life and evaluate whether semaglutide exposure causes long-term changes in metabolism or feeding behaviour in offspring in adulthood. This project will deliver vital insight into the long-term effects of semaglutide use in pregnancy on long-term offspring health.