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; 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.

在过去的十年中，在降低婴儿的发病率和死亡率方面取得了巨大进展 围产期。但是，在同一时期，减少母亲风险因素的工作减少了 与出生有关的健康和健康并发症。使用出生干预措施，例如归纳或 通过外源性催产素或通过剖宫产递送的劳动增强，稳步上升了近30 在美国的几年和这些干预措施最近与更高的发展风险有关 产后抑郁症（PPD）。两种干预措施都涉及改变神经肽催产素的水平和 催产素受体在新妈妈中的功能本身与较高的发展风险有关 ppd。该建议旨在探讨这些常见的出生干预对催产素改变的后果 具有特定假设的系统功能：（a）催产素受体基因OXTR，OXTR的表观遗传调节 孕产妇大脑的妊娠变化，可以通过DNA甲基化和 羟甲基化，（b）阴道出生作用于重置OXTR的表观遗传调节为妊娠前的表观遗传调节 州，（c）人为较高水平的催产素（劳动诱导）的出生会在早期的表观遗传转移中发生 OXTR回到孕前状态，对孕产妇护理和抑郁症的影响，相反（D） 人为地分娩了催产素（剖宫产） 调节回到孕前状态，再次导致孕产妇行为的变化和风险增加 对于PPD。 R01父母赠款提供了一个表观遗传时间表，以使孕产妇大脑整个妊娠以及进入 产后时期并评估常见的出生干预措施对该时间表的影响。我们开发了一个 动物模型（Prairie Vole）研究孕产妇大脑，并在完成样品方面取得了长足的进步 在赠款的第1和2年内收集，随着我们进入第3年，我们准备开始分子分析。这 格兰特和与之相关的分子工作为有兴趣的学生提供了绝佳的培训机会 在翻译科学中，尤其是一个不可思议的机会，可以跨越未来的护士科学家 兴趣在于孕产妇的心理健康，并减轻其对后代健康的影响。麦当劳女士将获得 理解，评估和应用表观遗传标记的技能，以在现实世界的孕产妇护理中工作 心理健康。通过这项培训，她将准备通过应用我们的工作来开始精确健康的职业 已经训练了她在动物模型中进行人类样品。我们有能力结合多样性 补充更广泛的研究计划，完成补充是非常可行的 在父母赠款的时间范围内进行项目。