Premature babies are at risk of death from immature lung development. For this reason, pregnant mothers at risk for preterm delivery are administered dexamethasone (DEX), a synthetic glucocorticoid that promotes fetal lung development. However, exposure to DEX in utero is associated with low birth weight and cardiovascular development pathologies. Moreover, our lab found that DEX administration in-utero leads to a sex-specific increase in stress-induced tachycardia in female, but not male offspring. This project seeks to expand on this preliminary finding of the heart by examining local effectors of activity from the sympathetic system (tyrosine hydroxylase and catechol-o-methyltransferase). Tyrosine hydroxylase was measured as it catalyzes the rate limiting step of norepinephrine synthesis while catechol-O- methyltransferase was studied as it catalyzes the degradation of norepinephrine. Acetylcholinesterase was used to measure parasympathetic activity as it catalyzes the degradation of the primary neurotransmitter of the parasympathetic nervous system, acetylcholine. Analyses of sympathetic as well as parasympathetic activity were done to determine influences of in-utero DEX exposure on autonomic regulation in adulthood. Pregnant rats were administered DEX (0.4 mg/kg, i.p.) or vehicle (20% w/v 2-hydroxypropyl ß- cyclodextran) at gestation days 18-21, with euthanasia of offspring occurring at around the time the offspring reached 13-15 weeks of age. Left ventricles and right atria were pulverized, processed and subjected to western blot analysis to determine expression of proteins of interest. Males exposed to DEX in-utero saw a decrease in tyrosine hydroxylase expression in left ventricle and right atrium when compared to vehicle control, a difference not seen with females. In addition, catechol-o-methyltransferase expression was increased in right atria from male, but not female rats. Acetylcholinesterase expression was reduced in the right atria of female, but not male rats. The present findings suggest reduced norepinephrine signaling in the heart of male, but not female DEX-exposed offspring. Given that we have previously found that female, but not male rats exhibit exaggerated stress-induced tachycardia, our current findings suggest that males possess a sex-specific compensatory mechanism allowing the heart to resist increased sympathetic signaling from the brain, one that females do not possess. The underlying mechanics of this proposed mechanism are unclear, and further investigation is needed in this subject to determine the significance of the findings from our study.

Stress and stress-related disorders increase the risk of Alzheimer’s Disease (AD) later in life. Some evidence suggests that prenatal maternal stress (PMS) can exacerbate AD. However, the effects of PMS on AD have not been as well studied. Epigenetic changes have been shown to contribute to AD and this is a possible mechanism by which PMS could accelerate AD. Thus, the present study aimed to investigate the effects of PMS on histone modifications, which change gene expression through alterations made to chromatin structure and thereby DNA accessibility. We utilized female 3xTG-AD mice and performed spatial and learning memory assessments between 5 and 6 months of age. Tissue was analyzed for AD pathology and epigenetic markers at 6 months of age were assessed PMS was shown to influence histone modifications H3K4me3 and H3K27me3 in a manner known to promote the expression of genes associated with neurodegeneration. Further, PMS impaired spatial memory, and, interestingly, the data resembled the pattern of H3K4me3 expression across groups, suggesting that this epigenetic modification could modulate the learning and memory effects of PMS. While the presence of hallmark AD pathologies were not accelerated by PMS, PMS did increase early tau phosphorylation events. Thus, this evidence suggests that PMS impairs spatial memory through epigenetic modifications and may potentially exacerbate AD later in life.