This application is a request for diversity supplemental funding for Ms. Monique Martinez to initiate her graduate studies in the laboratory of Dr. Taben Hale at the University of Arizona. This project examines the fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, an important system for regulating and coordinating adrenal glucocorticoid (GC) secretion to allow for proper adaptation to stressors and maintain physiological homeostasis. As part of the U54 program that oversees this project, Ms. Martinez will be a member of the training program and be exposed to the educational mission that the SCORE program is developing. Ms. Martinez will also work closely with the other PIs in the SCORE program. This includes Dr. Jill Goldstein who is mPI of the Program and the Lead of Project 1 and Dr. Stuart Tobet who is mPI of the program and PI of project 3. During development, increased exposure to GCs through prenatal stress or inflammation can disrupt fetal brain programming and increase risk for long-term health consequences. The foundation for this hypothesis is that the in-utero environment programs the brain and increases the risk developing long-term complex diseases in adulthood. Diseases with fetal origins include depression and anxiety-like disorders, social impairments, and cardiometabolic disorders. Common to each of these, is a dysregulation of the autonomic nervous system. The overarching goal of Ms. Martinez’ project is to examine the effects of in utero overexposure to GCs and inflammation on hypothalamic and cardiac development resulting in autonomic dysregulation. Preliminary data has shown that rodents display cardiovascular and behavioral changes after in utero exposure to the synthetic GC, dexamethasone (DEX). Specifically, late gestation exposure to DEX results in female-biased autonomic dysregulation that is characterized by an increase in sympathetic and a withdrawal of parasympathetic input to regulation of heart rate and blood pressure under basal and stress conditions. Healthy females have been shown to show a greater reliance on parasympathetic input, as compared to males. Preliminary findings suggest that prenatal DEX disrupts this normal development. Puberty is known to be a critical developmental period for programming of the autonomic nervous system. Therefore, studies outlined in this proposal test the hypothesis that puberty is a critical period for programing autonomic nervous system, and that late gestation perturbations negatively impact these responses. Autonomic function will be assessed in rats exposed to excess glucocorticoids (DEX) or inflammation (TLR7 agonist, resiquimod) in utero pre- (3-4 weeks of age) and post-puberty (8-10 weeks of age). To determine the degree to which these effects are peripherally mediated, cardiac responses to sympathetic and parasympathetic nervous system agonists will be evaluated ex vivo to remove any neural influences and reflex responses. These studies will have impli...