Maternal mediators of fetal growth restriction linked to prenatal alcohol exposure
胎儿生长受限的母体介导因素与产前酒精暴露有关
基本信息
- 批准号:10460854
- 负责人:
- 金额:$ 66.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-20 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAlcohol abuseAlcohol consumptionAlcoholismAlcoholsBiologicalBirthBlood CirculationBrainC-reactive proteinCell Culture TechniquesCell LineCellsChildChorionic villiCytokine Network PathwayDataDefectDevelopmental DisabilitiesDiagnosisDiagnosticDrug or chemical Tissue DistributionEndocrineEpithelialEthanolEtiologyExhibitsExposure toFamilyFetal Alcohol ExposureFetal Alcohol Spectrum DisorderFetal GrowthFetal Growth RetardationFunctional disorderGene ExpressionGoalsGrowthHead circumferenceHeightHumanHuman Cell LineInfantInjectionsInstitutesInterventionLinkLipoproteinsMeasuresMediatingMediator of activation proteinMesenchymalMicroRNAsMothersMusOutcomeOutcome StudyPathologyPathway interactionsPlacentaPlacental InsufficiencyPlacentationPlasmaPre-EclampsiaPregnancyPregnancy ComplicationsPregnant WomenPremature BirthProcessResearch PersonnelReview LiteratureRisk FactorsRodentRoleSamplingSchool-Age PopulationSecond Messenger SystemsSecond Pregnancy TrimesterSignal TransductionSpontaneous abortionStrategic PlanningSubgroupTestingUkraineUltrasonographyVascular Endothelial Growth FactorsWeightWomanalcohol consequencesalcohol exposurealcohol misusebasecohortcytokinedisabilityextracellularextracellular vesiclesfetalinhibitorinnovationmimeticsmouse modelnonhuman primatenovelparticlepregnantprenatal exposurepreventreceptorrecruitresponseskillstranscriptomicstranslational potentialtrophoblast
项目摘要
Project Summary/Abstract
Prenatal Alcohol Exposure (PAE) is a common cause of fetal growth restriction (FGR), which is
a known risk factor for brain disability. Our previous studies identified extracellular maternal
miRNAs as a causal link between PAE and FGR. These studies in pregnant women in Ukraine,
resulted in discovery of 11 miRNAs (HEamiRNAs) that were elevated in plasma of heavy alcohol-
exposed mothers who subsequently delivered growth-restricted, alcohol-affected infants (HEa),
but not in exposed mothers who delivered infants that were apparently unaffected (HEua), or
unexposed (UE) mothers. Maternal HEamiRNAs collectively explained 24-31% of the variance in
infant height, weight and head circumference at birth, and in rodents, non-human primates, and
in human trophoblast cell lines, explained PAE inhibition of placental trophoblast epithelial-
mesenchymal transition (EMT) and FGR. Studies in this proposal, test an innovative hypothesis
that two candidate cytokines, also identified in the Ukraine cohort, and extracellular miRNAs,
control fetal growth in response to PAE, and that these may be manipulated to overcome FGR.
In Aim 1, we test the hypothesis that two PAE-sensitive cytokines, C-reactive protein and sFlt1,
control HEamiRNA transfer between maternal circulation and trophoblasts, as a means to inhibit
the growth of chorionic villi, leading to FGR. Aim 2 is based on initial studies that showed 3
HEamiRNAs, which were elevated in both preeclampsia and FGR, promoted EMT gene expression
in trophoblasts. We plan to test the hypotheses that cytokines, and sub-groups of birth outcome-
defined HEamiRNAs may be manipulated to overcome FGR. Studies in Aims 1 and 2 will use cell
culture and mouse models, with ultrasound imaging and transcriptomic studies, to assess the role
of cytokines and HEamiRNAs in PAE-mediated inhibition of placental and fetal growth. In Aim 3,
we will assess associations between HEamiRNAs, and other conditions linked to defects in placental
development and function (preeclampsia, pre-term birth, spontaneous abortion, FGR), in
samples from pregnant women recruited in the San Diego region with and without evidence of
placental dysfunction, including PAE. We will additionally investigate the distribution HEamiRNAs
in lipoprotein particles (LPPs) and extracellular vesicles (EVs) to determine whether pregnancy
and/or placental dysfunction is associated with re-distribution of HEamiRNAs among extracellular
compartments, possibly influencing their endocrine function and target tissue distribution.
The proposed studies, led by qualified investigators with complementary skills, meet a significant
need for mechanism-centered diagnoses and intervention for pregnancy complications due to
PAE and other etiologies.
项目摘要/摘要
产前酒精暴露(PAE)是胎儿生长限制(FGR)的常见原因,
大脑残疾的已知危险因素。我们以前的研究确定了细胞外孕妇
miRNA作为PAE和FGR之间的因果关系。这些研究在乌克兰的孕妇,
导致发现了11个miRNA(heamirnas),这些miRNA(heamirnas)升高在重醇的血浆中
裸露的母亲随后交付了受限制性饮酒的婴儿(HEA),
但是,没有在暴露的母亲中,这些母亲送给显然不受影响的婴儿(heua)或
未受暴露的(UE)母亲。母亲的Heamirnas共同解释了24-31%的差异
出生时的婴儿身高,体重和头围,啮齿动物,非人类灵长类动物和
在人类滋养细胞细胞系中,解释了PAE抑制胎盘滋养细胞上皮
间充质转变(EMT)和FGR。在该提案中的研究,检验创新的假设
在乌克兰队列中也发现了两个候选细胞因子和细胞外miRNA,
控制胎儿生长对PAE的响应,并且可以操纵这些生长以克服FGR。
在AIM 1中,我们检验了两个对PAE敏感的细胞因子C反应蛋白和SFLT1的假设,
对照heamirna在母体循环和滋养细胞之间的转移,以此作为抑制的一种手段
绒毛膜的增长,导致FGR。 AIM 2基于最初的研究,该研究显示3
在先兆子痫和FGR中均升高的heamirnas促进了EMT基因表达
在滋养细胞中。我们计划测试细胞因子和出生结局的亚组的假设 -
可以操纵定义的Heamirnas以克服FGR。目标1和2中的研究将使用单元格
具有超声成像和转录组研究的培养和小鼠模型,以评估角色
PAE介导的胎盘生长的抑制作用中的细胞因子和HeamiRNA的摄氏。在AIM 3中,
我们将评估Heamirnas与与胎盘缺陷有关的其他条件之间的关联
开发和功能(子痫前期,预期出生,自发流产,FGR),
来自圣地亚哥地区招募的孕妇的样本,没有证据
胎盘功能障碍,包括PAE。我们还将调查分布heamirnas
在脂蛋白颗粒(LPP)和细胞外囊泡(EV)中,以确定是否怀孕
和/或胎盘功能障碍与细胞外heamirnas的重新分布有关
隔室,可能影响其内分泌功能和靶组织分布。
拟议的研究由具有互补技能的合格调查员领导,符合重要的研究
需要以机制为中心的诊断和干预妊娠并发症
PAE和其他病因。
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 }}
CHRISTINA CHAMBERS其他文献
CHRISTINA CHAMBERS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('CHRISTINA CHAMBERS', 18)}}的其他基金
Whole Body Effects of PAE Across the Life Span: Early Markers of & Clinical Interventions for Children and Adolescents in Ukraine
PAE 对整个生命周期的全身影响:早期标志
- 批准号:
10682611 - 财政年份:2022
- 资助金额:
$ 66.3万 - 项目类别:
Whole Body Effects of PAE Across the Life Span: Early Markers of & Clinical Interventions for Children and Adolescents in Ukraine
PAE 对整个生命周期的全身影响:早期标志
- 批准号:
10470647 - 财政年份:2022
- 资助金额:
$ 66.3万 - 项目类别:
Maternal mediators of fetal growth restriction linked to prenatal alcohol exposure
胎儿生长受限的母体介导因素与产前酒精暴露有关
- 批准号:
10706480 - 财政年份:2022
- 资助金额:
$ 66.3万 - 项目类别:
The Healthy Brain and Child Development National Consortium Administrative Core
健康大脑和儿童发展国家联盟行政核心
- 批准号:
10380522 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes
母乳喂养母亲的抗生素治疗:对乳汁、微生物组和婴儿结局的影响
- 批准号:
10309709 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
The Healthy Brain and Child Development National Consortium Administrative Core
健康大脑和儿童发展国家联盟行政核心
- 批准号:
10770941 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
The Healthy Brain and Child Development National Consortium Administrative Core
健康大脑和儿童发展国家联盟行政核心
- 批准号:
10494199 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes
母乳喂养母亲的抗生素治疗:对乳汁、微生物组和婴儿结局的影响
- 批准号:
10487495 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes
母乳喂养母亲的抗生素治疗:对乳汁、微生物组和婴儿结局的影响
- 批准号:
10681292 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
The Healthy Brain and Child Development National Consortium Administrative Core
健康大脑和儿童发展国家联盟行政核心
- 批准号:
10748764 - 财政年份:2021
- 资助金额:
$ 66.3万 - 项目类别:
相似国自然基金
年龄与异质对酗酒影响的建模与分析
- 批准号:11861044
- 批准年份:2018
- 资助金额:39.0 万元
- 项目类别:地区科学基金项目
酗酒相关问题的建模及研究
- 批准号:11461041
- 批准年份:2014
- 资助金额:36.0 万元
- 项目类别:地区科学基金项目
酗酒者易患肺部感染及高致死率的发病机制研究
- 批准号:U1404814
- 批准年份:2014
- 资助金额:30.0 万元
- 项目类别:联合基金项目
与酗酒毒害性相关的细胞色素CYP2E1蛋白酶催化反应机理及动力学的理论研究
- 批准号:21273095
- 批准年份:2012
- 资助金额:78.0 万元
- 项目类别:面上项目
酗酒促发外伤性蛛网膜下腔出血的生物力学机制及其量化法医病理学鉴定的研究
- 批准号:30772458
- 批准年份:2007
- 资助金额:28.0 万元
- 项目类别:面上项目
相似海外基金
Developing and Evaluating a Positive Valence Treatment for Alcohol Use Disorder with Anxiety or Depression
开发和评估治疗伴有焦虑或抑郁的酒精使用障碍的正价疗法
- 批准号:
10596013 - 财政年份:2023
- 资助金额:
$ 66.3万 - 项目类别:
A rigorous test of dual process model predictions for problematic alcohol involvement
对有问题的酒精参与的双过程模型预测的严格测试
- 批准号:
10679252 - 财政年份:2023
- 资助金额:
$ 66.3万 - 项目类别:
Role of Lysosome Damage in ALD Pathogenesis
溶酶体损伤在 ALD 发病机制中的作用
- 批准号:
10668006 - 财政年份:2023
- 资助金额:
$ 66.3万 - 项目类别:
Identifying the Effects of Race-Related Stressors on Laboratory- Induced Stress and Craving among African Americans with Alcohol Use Disorder
确定种族相关压力源对患有酒精使用障碍的非裔美国人实验室诱发的压力和渴望的影响
- 批准号:
10664454 - 财政年份:2023
- 资助金额:
$ 66.3万 - 项目类别:
Proud to Quit (P2Q): A Person-centered mobile technology intervention for smoking cessation among transgender adults
自豪地戒烟(P2Q):以人为本的移动技术干预跨性别成年人戒烟
- 批准号:
10647479 - 财政年份:2023
- 资助金额:
$ 66.3万 - 项目类别: