Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs
产前金属混合物、胎儿生长和 MicroRNA 的作用
基本信息
- 批准号:10218179
- 负责人:
- 金额:$ 24.15万
- 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:2020-07-17 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdultAffectAir PollutionAwardBiological MarkersBirth WeightBloodBlood specimenBostonCaliberCaliforniaCardiovascular DiseasesComplementComplexComplex MixturesDataDevelopmentDietEarly identificationEducational workshopEnrollmentEnvironmental EpidemiologyEnvironmental Risk FactorEpidemiologyEpigenetic ProcessEquationExposure toFeedbackFemurFetal DevelopmentFetal GrowthGene ExpressionGenesGestational AgeGoalsGrowthGrowth and Development functionHead circumferenceHealthHispanicsIndividualInvestigationKnowledgeLeadLearningLengthLifeLinkLos AngelesLow Birth Weight InfantLow incomeMeasurementMeasuresMediatingMentorsMetal exposureMetalsMethodsMicroRNAsModelingMorbidity - disease rateMothersNewborn InfantNon-Insulin-Dependent Diabetes MellitusOutcomePatternPerinatologyPhasePlacentaPlasmaPlayPopulationPositioning AttributePregnancyResearchResearch PersonnelRisk FactorsRoleSiteSourceStructureSumTimeToxic effectTrainingUltrasonographyUmbilical Cord BloodUnited StatesUniversitiesUrineWeightWeights and MeasuresWomanadverse outcomebasecigarette smokecirculating microRNAcohortdrinking waterenvironmental stressorepigenomeexperiencefetalimprovedin uteroinfancymRNA Expressionmetal poisoningmortalitynovelpollutantprenatalprenatal exposurepreventprogramspublic health interventionsocial stressortoxic metaltraining opportunitytranscriptome sequencing
项目摘要
PROJECT SUMMARY/ABSTRACT
Reduced fetal growth has been implicated in a broad range of adverse health outcomes. Growing evidence
suggests that toxic metal exposures adversely affect fetal growth, indicated by reduced fetal ultrasound
measurements and lower birth weight. Although most individuals are exposed simultaneously to multiple
metals, which may act additively or synergistically to reduce fetal growth, the majority of studies have focused
on the toxicity of individual metals. While the mechanisms underlying metal-induced reductions in fetal growth
are incompletely understood, there is evidence that epigenetic dysregulation, including altered microRNA
(miRNA) expression, contributes to these effects. In addition to epigenetically regulating gene expression,
maternal circulating miRNAs play important roles in maternal-placental-fetal crosstalk. However, the potential
role of maternal circulating miRNAs in mediating metal mixture effects on fetal growth is unknown. The goal of
the proposed project is to examine the impact of prenatal metal mixture exposures on fetal growth and to
determine whether altered maternal circulating miRNAs mediate these relationships. During the mentored K99
phase of this award, Dr. Howe will leverage existing data and biospecimens from 500 mother-newborn pairs in
the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, a low-
income predominately Hispanic pregnancy cohort based in Los Angeles, to investigate potential additive and
synergistic relationships between prenatal exposure to 15 metals and in utero growth and birth weight. To
accomplish this, she will expand metals exposure assessment in the MADRES pregnancy cohort and train in
methods for analyzing complex environmental mixtures, including weighted quantile sum regression and
Bayesian kernel machine regression. During the R00 phase, Dr. Howe will determine whether maternal
circulating miRNAs mediate metal mixture-fetal growth relationships, using structural equation models, and will
examine potential downstream effects by profiling mRNA expression levels within the maternal-placental-fetal
axis, using RNA-Seq, in a subset (N = 50) of mother-newborn pairs. Results from the proposed studies may be
used to improve the efficacy of public health interventions aimed at preventing metal-induced reductions in
fetal growth. Furthermore, they will increase knowledge of a potential underlying mechanism (altered maternal
circulating miRNAs) and may lead to the identification of early and relatively non-invasive biomarkers of metal
mixture exposures and reduced fetal growth. Dr. Howe has assembled a mentoring team, spanning the
University of Southern California, Boston University, and Emory University, with expertise in metals toxicity,
environmental mixtures modeling, epigenetic epidemiology, and perinatology. This team will provide ongoing
feedback and on-site training opportunities to complement coursework, workshops, and seminars, which will
support Dr. Howe’s transition to become an independent investigator with a research program that focuses on
the effects of early life metal mixture exposures on the epigenome and fetal growth.
项目摘要/摘要
胎儿生长发育减退已牵涉到一系列不良健康后果。越来越多的证据
表明有毒金属暴露对胎儿生长发育有不利影响,这表明胎儿超声降低。
测量和较低的出生体重。尽管大多数人同时接触到多个
金属,它可以相加或协同作用来减少胎儿生长,大多数研究都集中在
关于单个金属的毒性。虽然金属导致胎儿生长减慢的机制
都不完全了解,有证据表明表观遗传失调,包括改变的microRNA
(MiRNA)表达,有助于这些效应。除了表观遗传调控基因表达外,
母体循环中的miRNAs在母体-胎盘-胎儿串扰中起着重要作用。然而,潜在的
母亲循环中的miRNAs在调节金属混合物对胎儿生长的影响中的作用尚不清楚。的目标是
拟议的项目是研究产前接触金属混合物对胎儿生长发育的影响,并
确定母体循环中改变的miRNAs是否调节了这些关系。在被指导的K99期间
在这个奖项的阶段,豪博士将利用现有的数据和来自500对母婴的生物标本
来自环境和社会应激源的母亲和发育风险(MADRES)研究,一项低成本的
收入主要是西班牙裔怀孕队列,总部设在洛杉矶,以调查潜在的附加物和
产前接触15种金属与宫内生长和出生体重之间的协同关系。至
为此,她将在Madres怀孕队列中扩大金属暴露评估,并在
分析复杂环境混合物的方法,包括加权分位数和回归和
贝叶斯核机回归。在R00阶段,豪医生将确定母体
使用结构方程模型,循环中的miRNAs调节金属混合物-胎儿生长关系,并将
通过分析母体-胎盘-胎儿内的mRNA表达水平来检查潜在的下游影响
轴,使用RNA-Seq,在母亲-新生儿对的子集(N=50)中。拟议研究的结果可能是
用于提高公共卫生干预措施的有效性,旨在防止金属引起的
胎儿发育。此外,它们将增加对潜在潜在机制(母体改变)的了解
循环中的miRNAs),并可能导致早期和相对非侵入性的金属生物标志物的识别
混合暴露和降低胎儿生长发育。豪博士组建了一个指导团队,横跨
南加州大学、波士顿大学和埃默里大学,拥有金属毒性方面的专业知识,
环境混合模型、表观遗传流行病学和围产儿学。该团队将提供持续的
反馈和现场培训机会,以补充课程作业、研讨会和研讨会,这将
支持豪博士转型为一名独立调查员,其研究计划侧重于
生命早期金属混合物暴露对表观基因组和胎儿生长的影响。
项目成果
期刊论文数量(0)
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Caitlin Grace Howe其他文献
Caitlin Grace Howe的其他文献
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{{ truncateString('Caitlin Grace Howe', 18)}}的其他基金
Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs
产前金属混合物、胎儿生长和 MicroRNA 的作用
- 批准号:
10452576 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs
产前金属混合物、胎儿生长和 MicroRNA 的作用
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10202881 - 财政年份:2020
- 资助金额:
$ 24.15万 - 项目类别:
Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs
产前金属混合物、胎儿生长和 MicroRNA 的作用
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9917770 - 财政年份:2019
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Influences of arsenic and folate on histone methylation marks
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- 批准号:
8982481 - 财政年份:2015
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$ 24.15万 - 项目类别:
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