Mechanisms of maternal brain changes with birth interventions

在过去十年中，中国在降低婴儿发病率和死亡率方面取得了很大进展。 围产期。然而，在同一时间段内，为减少产妇风险因素所做的工作较少。 用于治疗与分娩相关的健康和健康并发症。分娩干预措施的使用，如引产或 使用外源性催产素或通过剖腹产分娩的人数在近30年里稳步上升 这些干预措施最近被认为与更高的发病风险有关 产后抑郁症(PPD)。这两种干预措施都涉及改变神经肽催产素和 新妈妈的催产素受体的功能，这本身已被认为与更高的发展风险有关 PPD。该提案旨在探讨这些常见的生育干预措施对催产素变化的影响。 系统功能，有特定的假设：(A)催产素受体基因的表观遗传调节，OXTR， 在怀孕期间母体大脑的变化，可以通过DNA甲基化和 羟甲基化，(B)阴道分娩将OXTR的表观遗传调控重置为怀孕前 国家，(C)人为较高的催产素水平(引产)在出生时会产生较早的表观遗传学转变 OXTR恢复到孕前状态，导致产妇护理和抑郁，反之亦然(D) 人为降低催产素水平的分娩(剖腹产)会阻止OXTR的出生后及时转移 监管回到怀孕前的状态，再次导致母亲行为的变化和风险增加 为PPD做准备。 R01父母赠款提供了一个表观遗传学的时间表，可以让母亲的大脑在怀孕期间和 并评估常见生育干预措施对这一时间线的影响。我们开发了一种 研究母体大脑的动物模型(草原田鼠)，在完成样本方面取得了很大进展 在拨款的第一年和第二年收集，随着我们进入第三年，我们准备开始分子分析。这 格兰特及其相关的分子工作为感兴趣的学生提供了一个极好的培训机会 在翻译科学方面，特别是一个令人难以置信的机会交叉培训一位未来的护士科学家 人们的兴趣在于产妇的心理健康和减轻其对后代健康的影响。麦克唐纳女士将获得 理解、评估和应用表观遗传标记在现实世界中的孕产妇保健和 心理健康。通过这次培训，她将准备好通过应用我们的工作在精确健康领域开始职业生涯 曾训练过她在动物模型中做人体样本。我们做好了充分的准备，将多样性 补充工作纳入更广泛的研究方案，完成补充工作具有很高的可行性 在上级拨款的时间范围内完成项目。

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.