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
受孕前的母亲压力与不良代谢和神经发育有关
对孩子的影响。我们成长的环境为我们一生的身心健康奠定了基础
健康。在整个发育过程中,快速生长和系统可塑性使器官系统对
环境因素的影响可以赋予适应性优势或持久的脆弱性。有
我们对孕期期间孕产妇压力相关机制的理解存在根本差距
儿童逆境风险增加的孕前期。母亲压力可能产生的具体影响
涉及胎儿和母体因素之间复杂的相互作用,表观遗传修饰肯定会发挥作用
在这些过程中表现突出。该提案的中心假设是,怀孕期间母亲的压力
孕前期将通过皮质醇的改变来改变卵泡内的分子环境
水平、代谢和基因表达,最终影响卵母细胞和胚胎质量
总体上并通过 DNA 甲基化涉及影响终生健康和
后代的健康。由于这些研究无法在人类身上进行,并且啮齿动物模型缺乏
为了回答这些问题的复杂性,我们将利用非人类灵长类动物模型。恒河猴的用途
通过压力干预和完善的方法来研究卵泡发生提供了精确度
已被验证用于发展规划的研究。我们将描述先入为主的影响
对卵母细胞质量的压力;皮质醇、代谢标志物和卵巢卵泡微基因表达
环境;以及所得卵母细胞和胚胎中的 DNA 甲基化。采用独特的纵向设计,我们
将检查自然和人工刺激循环中的这些变化并采用尖端技术
这将允许评估单个卵泡内的材料来检验我们的假设。这部作品是
可能会显着推动该领域朝着确定可改变的根本原因和调解因素的目标迈进
通过产妇压力促进孕前发展规划并提出目标
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
CHARLES L CHAFFIN其他文献
CHARLES L CHAFFIN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
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:
7715596 - 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:
相似海外基金
Gastrin Regulation of Gastric Antral Stem and Corpus Progenitor Cells
胃窦干细胞和胃体祖细胞的胃泌素调节
- 批准号:
10490463 - 财政年份:2021
- 资助金额:
$ 65.43万 - 项目类别:
Gastrin Regulation of Gastric Antral Stem and Corpus Progenitor Cells
胃窦干细胞和胃体祖细胞的胃泌素调节
- 批准号:
10686228 - 财政年份:2021
- 资助金额:
$ 65.43万 - 项目类别:
Gastrin Regulation of Gastric Antral Stem and Corpus Progenitor Cells
胃窦干细胞和胃体祖细胞的胃泌素调节
- 批准号:
10367556 - 财政年份:2021
- 资助金额:
$ 65.43万 - 项目类别:
CAPLA Study: Catheter ablation for persistent atrial fibrillation. A Multicentre randomised study of pulmonary vein antral isolation (PVAI) alone vs PVAI with posterior Left Atrial wall isolation (PWI)
CAPLA 研究:导管消融治疗持续性心房颤动。
- 批准号:
nhmrc : 1134023 - 财政年份:2017
- 资助金额:
$ 65.43万 - 项目类别:
Postgraduate Scholarships
CAPLA Study: Catheter ablation for persistent atrial fibrillation. A Multicentre randomised study of pulmonary vein antral isolation (PVAI) alone vs PVAI with posterior Left Atrial wall isolation (PWI)
CAPLA 研究:导管消融治疗持续性心房颤动。
- 批准号:
nhmrc : GNT1134023 - 财政年份:2017
- 资助金额:
$ 65.43万 - 项目类别:
Postgraduate Scholarships
Markers of oocyte developmental potential during antral and ovulatory follicle stages
窦状卵泡和排卵卵泡阶段卵母细胞发育潜力的标志物
- 批准号:
451308-2013 - 财政年份:2016
- 资助金额:
$ 65.43万 - 项目类别:
Industrial Postgraduate Scholarships
Markers of oocyte developmental potential during antral and ovulatory follicle stages
窦状卵泡和排卵卵泡阶段卵母细胞发育潜力的标志物
- 批准号:
451308-2013 - 财政年份:2015
- 资助金额:
$ 65.43万 - 项目类别:
Industrial Postgraduate Scholarships
Markers of oocyte developmental potential during antral and ovulatory follicle stages
窦状卵泡和排卵卵泡阶段卵母细胞发育潜力的标志物
- 批准号:
451308-2013 - 财政年份:2014
- 资助金额:
$ 65.43万 - 项目类别:
Industrial Postgraduate Scholarships
Effect of postpartum resumption of ovarian activity on the formation of antral follicle-like structures by bovine cumulus-oocyte complexes in Holstein cows.
产后恢复卵巢活性对荷斯坦奶牛卵丘-卵母细胞复合物形成窦卵泡样结构的影响。
- 批准号:
26870406 - 财政年份:2014
- 资助金额:
$ 65.43万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Markers of oocyte developmental potential during antral and ovulatory follicle stages
窦状卵泡和排卵卵泡阶段卵母细胞发育潜力的标志物
- 批准号:
451308-2013 - 财政年份:2013
- 资助金额:
$ 65.43万 - 项目类别:
Industrial Postgraduate Scholarships