Mechanisms of maternal brain changes with birth interventions

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Great progress has been made over the past decade in reduction of infant morbidity and mortality in the perinatal period. During this same time period, however, less work has been done to reduce maternal risk factors for health and wellness complications associated with birth. The use of birth interventions, such as induction or augmentation of labor with exogenous oxytocin or delivery via cesarean section, has risen steadily for nearly 30 years in the United States and these interventions have recently been linked to a higher risk for development of postpartum depression (PPD). Both interventions involve altering the levels of the neuropeptide oxytocin and functioning of the oxytocin receptor in new mothers, which has itself been linked to a higher risk for developing PPD. This proposal aims to explore the consequences of these common birth interventions on altered oxytocin system functioning, with specific hypotheses: (a) that epigenetic regulation of the oxytocin receptor gene, OXTR, changes across gestation in the maternal brain and can be indexed by measures of DNA methylation and hydroxymethylation, (b) that vaginal birth acts to reset epigenetic regulation of OXTR back to pre-pregnancy states, (c) that birth with artificially higher levels of oxytocin (labor induction) creates an earlier epigenetic shift in OXTR back to a pre-pregnancy state, with consequences for maternal care and depression, and conversely (d) that births with artificially lower levels of oxytocin (cesarean sections) prevent the timely postnatal shift in OXTR regulation back to a pre-pregnancy state, again leading to changes in maternal behavior and an increased risk for PPD. The R01 parent grant provides an epigenetic timeline for change in the maternal brain across gestation and into the postnatal period and assesses the impact of common birth interventions to this timeline. We developed an animal model (prairie vole) to study the maternal brain and have made great progress in completing sample collection in years 1 and 2 of the grant, as we move into year 3 we are poised to begin molecular analysis. This grant and the molecular work associated with it provides an excellent training opportunity for students interested in translational science, and in particular an incredible opportunity to cross-train a future nurse scientist whose interests lie in maternal mental health and mitigating its effects on offspring health. Ms. McDonald will obtain skills in understanding, assessing and applying epigenetic markers to work in real world maternal care and mental health. With this training she will be poised to begin a career in precision health by applying the work we have trained her to do in an animal model to human samples. We are well positioned to incorporate the diversity supplement work into the broader program of research, and it is highly feasible to complete the supplement project within the timeframe of the parent grant.