Preconception Stress Effects on Oogenesis
孕前应激对卵子发生的影响
基本信息
- 批准号:9917282
- 负责人:
- 金额:$ 65.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntralAttention deficit hyperactivity disorderBehavioralCell physiologyChildChild HealthComplexConceptionsConsensusCouplesCritical PathwaysDNA MethylationDevelopmentDiabetes MellitusDiseaseEmbryoEmbryonic DevelopmentEnvironmentEnvironmental Risk FactorEpigenetic ProcessEstradiolEvaluationExposure toFertilityFertilizationFertilization in VitroFetal DevelopmentFollicular FluidFoundationsFutureGene ExpressionGenesGlucoseGlycolysisGoalsHealthHealth behaviorHormonesHumanHydrocortisoneHypertensionImmuneImpairmentIndividualInterventionLife StyleMacaca mulattaMeasurableMediator of activation proteinMedicalMental HealthMetabolicMetabolic MarkerMetabolismMethodsMethylationModelingModificationMolecularMolecular AnalysisMusNeurologicNeurosecretory SystemsObesityOocytesOogenesisOutcomeOvarianOvarian FolliclePhasePhysiologicalPlant RootsPregnancyPreventionPrevention strategyProcessProductionPsychosocial StressRecommendationReportingReproducibilityResearchResearch DesignRetrievalRiskRodent ModelRoleSamplingStressSystemTechnologyTestingTimeTissuesTranslatingUp-RegulationWomanWorkautism spectrum disorderblastocystbody systemchildhood adversitycritical perioddiscrete timeembryo qualityexperiencefatty acid oxidationfetalfolliculogenesisgenome wide methylationglucose metabolismgranulosa cellhypothalamic-pituitary-adrenal axisinnovationlongitudinal designmaternal stressmethylation patternmethylomenonhuman primateoffspringoocyte maturationoocyte qualityphysical conditioningpsychologicrapid growthresponse
项目摘要
ABSTRACT
Maternal stress prior to conception has been associated with adverse metabolic and neurodevelopmental
outcomes in the child. The milieu in which we develop lays the foundation for a lifetime of physical and mental
health. Throughout development, rapid growth and system plasticity render organ systems sensitive to the
effects of environmental factors that can confer adaptive advantages or lasting vulnerability. There are
fundamental gaps in our understanding of the mechanisms that connect maternal stress during the
preconception period with enhanced risk for childhood adversity. Specific effects of maternal stress likely
involve a complex interaction between fetal and maternal factors, and epigenetic modification is sure to feature
prominently in these processes. The central hypothesis of this proposal is that maternal stress during the
preconception period will alter the intrafollicular molecular environment through alterations in cortisol
levels, metabolism, and gene expression, with ultimate impacts on oocyte and embryo quality both
grossly and through DNA methylation involving critical pathways that influence lifelong health and
wellness in offspring. As these studies cannot be performed in humans and because rodent models lack the
complexity to answer these questions, we will utilize a nonhuman primate model. Use of the rhesus macaque
affords precision with a stress intervention and well-honed methods for the study of folliculogenesis that have
been validated for the study of developmental programming. We will characterize the effects of preconception
stress on oocyte quality; cortisol, metabolic markers and gene expression in the ovarian follicular micro-
environment; and DNA methylation in the resulting oocyte and embryo. Using a unique longitudinal design, we
will examine these changes in natural and artificially-stimulated cycles and employ cutting edge technology
that will allow for evaluation of materials within individual ovarian follicles to test our hypotheses. This work is
likely to move the field measurably towards the goal of identifying modifiable root causes and mediators that
contribute to preconception developmental programming through maternal stress and suggesting targets for
prevention strategies
抽象的
受孕之前的孕产妇压力与不良代谢和神经发育有关
孩子的结果。我们开发的环境为一生的身心奠定了基础
健康。在整个开发中,快速生长和系统可塑性使器官系统对
可以赋予适应性优势或持久脆弱性的环境因素的影响。有
我们对在孕产妇压力中的机制的理解中的基本差距
先入为主时期,童年逆境风险增加。孕产妇压力的特定影响可能
涉及胎儿和母体因素之间的复杂相互作用,并且表观遗传修饰肯定具有特征
在这些过程中显着。该提议的核心假设是
先选期会通过改变皮质醇的变化来改变流体内分子环境
水平,代谢和基因表达,对卵母细胞和胚胎质量产生最终影响
严重并通过DNA甲基化,涉及影响终身健康和的关键途径
后代健康。由于这些研究不能在人类中进行,并且由于啮齿动物模型缺乏
回答这些问题的复杂性,我们将利用非人类的灵长类动物模型。豪华猕猴的使用
通过应力干预和良好的方法提供精确的研究,以研究卵泡发生
已被验证用于研究发展节目。我们将表征先入之见的影响
压力卵母细胞质量;卵巢卵泡微微体中的皮质醇,代谢标记和基因表达
环境;以及所得的卵母细胞和胚胎中的DNA甲基化。使用独特的纵向设计,我们
将检查自然和人为刺激周期的这些变化,并采用尖端技术
这将允许评估各个卵巢卵泡中的材料来检验我们的假设。这项工作是
可能会以衡量可修改的根本原因和调解人的目标来衡量地将现场移动
通过孕产妇的压力为孕前的发展编程做出贡献,并提出目标的目标
预防策略
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHARLES L CHAFFIN其他文献
CHARLES L CHAFFIN的其他文献
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{{ truncateString('CHARLES L CHAFFIN', 18)}}的其他基金
Gluconeogenesis and Energy Substrates: Shifting Paradigms in the Primate Ovary
糖异生和能量底物:灵长类动物卵巢范式的转变
- 批准号:
8772431 - 财政年份:2014
- 资助金额:
$ 65.43万 - 项目类别:
Gluconeogenesis and Energy Substrates: Shifting Paradigms in the Primate Ovary
糖异生和能量底物:灵长类动物卵巢范式的转变
- 批准号:
8926698 - 财政年份:2014
- 资助金额:
$ 65.43万 - 项目类别:
MECHANISMS OF LUTEINIZATION IN THE PRIMATE OVARY
灵长类动物卵巢黄体化机制
- 批准号:
7959012 - 财政年份:2009
- 资助金额:
$ 65.43万 - 项目类别:
Role of mineralocorticoid receptor in primate ovarian function
盐皮质激素受体在灵长类动物卵巢功能中的作用
- 批准号:
7863779 - 财政年份:2009
- 资助金额:
$ 65.43万 - 项目类别:
Role of mineralocorticoid receptor in primate ovarian function
盐皮质激素受体在灵长类动物卵巢功能中的作用
- 批准号:
7471142 - 财政年份:2008
- 资助金额:
$ 65.43万 - 项目类别:
MECHANISMS OF LUTEINIZATION IN THE PRIMATE OVARY
灵长类动物卵巢黄体化机制
- 批准号:
7715596 - 财政年份:2008
- 资助金额:
$ 65.43万 - 项目类别:
Role of mineralocorticoid receptor in primate ovarian function
盐皮质激素受体在灵长类动物卵巢功能中的作用
- 批准号:
7665159 - 财政年份:2008
- 资助金额:
$ 65.43万 - 项目类别:
MECHANISMS OF LUTEINIZATION IN THE PRIMATE OVARY
灵长类动物卵巢黄体化机制
- 批准号:
7562182 - 财政年份:2007
- 资助金额:
$ 65.43万 - 项目类别:
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