Mechanisms of maternal brain changes with birth interventions

分娩干预对母亲大脑变化的机制

• 批准号: 10406415
• 负责人: CAROL SUE CARTER PORGES
• 金额: $ 7.74万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406415
• 关键词: Animal Model; Back; Birth; Brain; Caring; Cesarean section; DNA Methylation; Development; Epigenetic Process; Family; Functional disorder; Future; Grant; Health; Human; Induced Labor; Intervention; Labor augmentation; Link; Maternal Behavior; Measures; Mediating; Mental Depression; Mental Health; Molecular; Molecular Analysis; Mothers; Neuropeptides; Nurses; Oxytocin; Oxytocin Receptor; Play; Positioning Attribute; Postpartum Depression; Precision Health; Pregnancy; Receptor Gene; Regulation; Research; Risk; Risk Factors; Sampling; Scientist; Shapes; Students; System; Time; TimeLine; Training; Translational Research; United States; Vaginal delivery procedure; Work; career; epigenetic marker; epigenetic regulation; experience; high risk; indexing; infant morbidity/mortality; interest; maternal risk; offspring; parent grant; perinatal period; postnatal; postnatal period; prairie vole; prepregnancy; prevent; programs; role model; sample collection; skills; training opportunity

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.

过去十年来，在降低婴儿发病率和死亡率方面取得了巨大进展 围产期。然而，在同一时期，减少孕产妇危险因素的工作却较少 用于与出生相关的健康和保健并发症。使用分娩干预措施，例如引产或 近 30 年来，使用外源性催产素或剖腹产助产率稳步上升 在美国，这些干预措施最近与更高的发展风险有关 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 新妈妈催产素受体的功能，这本身就与较高的罹患风险有关 产后抑郁症。该提案旨在探讨这些常见的分娩干预措施对改变催产素的影响 系统功能，具有特定的假设：（a）催产素受体基因 OXTR 的表观遗传调控， 母体大脑在妊娠期间的变化，可以通过 DNA 甲基化的测量来索引 羟甲基化，(b) 阴道分娩可将 OXTR 的表观遗传调控重置回怀孕前状态 指出，(c) 人为地提高催产素水平（引产）的分娩会导致更早的表观遗传转变 OXTR 回到怀孕前状态，对孕产妇护理和抑郁产生影响，反之亦然 (d) 人为降低催产素水平的分娩（剖腹产）会阻碍 OXTR 的及时产后转变 调节回到怀孕前的状态，再次导致母亲行为的改变和风险的增加 对于产后抑郁症。 R01 家长资助提供了母体大脑从妊娠到成年的变化的表观遗传时间表。 产后期并评估常见分娩干预措施对该时间线的影响。我们开发了一个 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 资助的第一年和第二年收集，当我们进入第三年时，我们准备开始分子分析。这 资助和与之相关的分子工作为感兴趣的学生提供了极好的培训机会 在转化科学领域，特别是交叉培训未来护士科学家的绝佳机会 人们的兴趣在于母亲的心理健康并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孕产妇护理工作中的技能 心理健康。通过这次培训，她将准备好通过应用我们的工作开始精准健康的职业生涯 训练她在动物模型中对人体样本进行处理。我们有能力融入多样性 将补充工作纳入更广泛的研究计划，完成补充的可行性很高 在母公司拨款的时间范围内进行项目。