The Impact of Transgenerational Racial Trauma on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy. Comparisons Between Caucasian and African American Populations
跨代种族创伤对怀孕期间母婴二元体表观遗传修饰的影响。
基本信息
- 批准号:10710037
- 负责人:
- 金额:$ 61.63万
- 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:2022-09-25 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAdultAfricanAfrican AmericanAfrican American populationAfrican ancestryAwarenessBiologicalBiological MarkersBlack raceCellsChildChildhoodChromatin StructureChronicCivil RightsCrowsDevelopmentDiscriminationDisparityEducationEnvironmentEpigenetic ProcessExposure toFetal DevelopmentFetal Growth RetardationFetusFutureGene ExpressionGenerationsGenetic TranscriptionGenomic DNAHealthHealth PromotionImmuneImmune System DiseasesImmune responseImmunityImmunologicsInfantInfant HealthInfant MortalityInflammationInflammation MediatorsInflammatoryInheritance PatternsInheritedInterventionLinkMaternal HealthMaternal-Fetal ExchangeModificationMononuclearMothersPathologyPatternPersonal SatisfactionPhenotypePhysiologicalPlacentaPlacentationPopulationPre-EclampsiaPregnancyPregnancy OutcomePregnant WomenPremature BirthPropertyRaceRiskShapesSignal TransductionSocioeconomic StatusStandardizationStressStructural RacismSurveysTissuesTrainingTraumaUmbilical Cord BloodUnited StatesVisionVoting RightWomanadverse outcomebisulfite sequencingcaucasian Americancohortcomparativecytokinedigitalexperiencefetalfetal immunitygenetic signaturegenome-widegenomic platformhealth disparityimmune activationimmunoregulationin uteroinfancyinfant morbidityinfant morbidity/mortalityinflammatory markermaternal stressmortalitymultiple omicsnano-stringneonateperceived stressracial disparityresponsesystemic inflammatory responsetranscriptometranscriptome sequencingtranscriptomicstransgenerational epigenetic inheritancetransmission processwhole genome
项目摘要
Project Summary
Structural racism and discrimination (SRD) have remained a historical legacy of the U.S. from the beginning of
enslavement of African populations in 1619 to the era of apartheid (“Jim Crow”), which ended with the Civil and
Voting Rights Acts. Hidden in plain sight is the biological impact of racial trauma. There is an increasing
awareness that SRD is a salient mechanism perpetuating racial gaps in health among African Americans. In
particular, studies have documented the impact of SRD on negative pregnancy outcomes, including higher rates
of preterm birth among African American (AA) women and higher rates of mortality among Black mothers and
infants. These racial disparities in maternal and infant health are pervasive even after accounting for socio-
economic status and education; and have been shown to persist transgenerationally, possibly via epigenetic
influences. In this study, we seek to investigate the impact of race and transgenerational SRD-related trauma
among AA women on distinct epigenetic modifications at the maternal-fetal interface that are linked to altered
immune cell development, activation, and signaling in the placenta and developing fetus. Studies suggest that
the placenta may be the gateway of maternal transgenerational epigenetic inheritance. Mounting evidence
suggests the effects of in utero epigenetic changes go beyond influencing the mother and the child, and are
carried forward through adulthood into germline, to the detriment of successive generations. Perturbed placental
epigenetics is associated with intrauterine growth restriction, preterm birth, and pre-eclampsia, which are the
drivers of infant mortality among AA. Studies demonstrate race is associated with placental inflammatory
pathology. In addition, high rates of stress due to transgenerational trauma have been associated with chronic
inflammation at the placenta and poor pregnancy outcomes. However, the biological properties that shape
disparities in pregnancy outcomes remain unknown. We hypothesize that SRD-related trauma is transmitted
across generations and manifests with epigenetic inheritance patterns that promote inflammation and innate
immune dysfunction in the placenta and fetus. Three specific aims have been proposed: 1) Evaluate the burden
of SRD on maternal stress, systemic inflammation, and epigenetic signatures among AA pregnant women; 2)
Perform comparative transcriptional, epigenetic, and immunological profiling of placentae from AA and CA
pregnant women to identify specific alterations associated with SRD-related stress; and 3) Investigate in utero
programming of immune responses and the inheritance of specific epigenetic signatures in AA neonates
exposed to maternal SRD-related stress. The biological impact of SRD on epigenetic alterations at the placenta
may contribute to increased vulnerability towards preterm birth and adverse outcomes in infancy and childhood.
These studies may inform future interventions to address such health risks and can promote the health and well-
being of at-risk mother-infant pairs.
项目摘要
结构性种族主义和歧视(SRD)自世纪初以来一直是美国的历史遗产
1619年,非洲人口被奴役到种族隔离时代(“吉姆·克劳”),种族隔离以公民和
投票权法案。种族创伤的生物学影响隐藏在显而易见的地方。还有越来越
意识到SRD是非洲裔美国人健康方面种族差距持续存在的突出机制。在
特别是,研究记录了SRD对不良妊娠结局的影响,包括较高的发生率,
非裔美国人(AA)妇女的早产率和黑人母亲的死亡率较高,
婴儿。即使考虑到社会因素,孕产妇和婴儿健康方面的这些种族差异仍然普遍存在。
经济地位和教育;并已被证明持续转代,可能通过表观遗传
影响。在这项研究中,我们试图调查种族和跨代SRD相关创伤的影响,
在AA妇女中,母亲-胎儿界面上的不同表观遗传修饰与改变
免疫细胞的发育、活化和胎盘和发育中胎儿的信号传导。研究表明
胎盘可能是母体跨代表观遗传的门户。越来越多的证据
表明子宫内表观遗传变化的影响不仅仅是影响母亲和孩子,
通过成年期进入生殖细胞,对后代造成损害。胎盘扰动
表观遗传学与子宫内生长受限、早产和先兆子痫有关,这些是
AA中婴儿死亡率的驱动因素。研究表明种族与胎盘炎性相关
病理此外,由于跨代创伤造成的高压力率与慢性疾病有关。
胎盘炎症和不良妊娠结局。然而,塑造我们的生物特性
怀孕结果的差异仍然未知。我们假设SRD相关的创伤是通过
并表现出表观遗传模式,促进炎症和先天性
胎盘和胎儿的免疫功能紊乱提出了三个具体目标:1)评估负担
SRD对AA孕妇的母体压力、全身炎症和表观遗传特征的影响; 2)
对AA和CA的胎盘进行比较转录、表观遗传和免疫学分析
孕妇,以确定与SRD相关的压力相关的具体变化;和3)在子宫内调查
AA新生儿免疫应答的编程和特定表观遗传标记的遗传
承受着与母亲性冲动障碍有关的压力SRD对胎盘表观遗传学改变的生物学影响
可能会导致早产的风险增加,并对婴儿和儿童产生不利影响。
这些研究可以为未来的干预措施提供信息,以解决这些健康风险,并可以促进健康和良好的-
有风险的母婴配对。
项目成果
期刊论文数量(1)
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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Rana Chakraborty其他文献
Rana Chakraborty的其他文献
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{{ truncateString('Rana Chakraborty', 18)}}的其他基金
The Impact of Transgenerational Racial Trauma on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy. Comparisons Between Caucasian and African American Populations
跨代种族创伤对怀孕期间母婴二元体表观遗传修饰的影响。
- 批准号:
10523426 - 财政年份:2022
- 资助金额:
$ 61.63万 - 项目类别:
Next generation training in HIV research: Immunity in the First 1000 days in mother-infant dyads (TIGRIS)
下一代艾滋病毒研究培训:母婴二人最初 1000 天的免疫力 (TIGRIS)
- 批准号:
10594540 - 财政年份:2022
- 资助金额:
$ 61.63万 - 项目类别:
Next generation training in HIV research: Immunity in the First 1000 days in mother-infant dyads (TIGRIS)
下一代艾滋病毒研究培训:母婴二人最初 1000 天的免疫力 (TIGRIS)
- 批准号:
10471480 - 财政年份:2022
- 资助金额:
$ 61.63万 - 项目类别:
Mechanisms by which trophoblasts recruit T cells to the placental villi during maternal HIV and CMV co-infection
母体 HIV 和 CMV 合并感染期间滋养层将 T 细胞募集至胎盘绒毛的机制
- 批准号:
10080877 - 财政年份:2020
- 资助金额:
$ 61.63万 - 项目类别:
Mechanisms by which trophoblasts recruit T cells to the placental villi during maternal HIV and CMV co-infection
母体 HIV 和 CMV 合并感染期间滋养层将 T 细胞募集至胎盘绒毛的机制
- 批准号:
10223400 - 财政年份:2020
- 资助金额:
$ 61.63万 - 项目类别:
How maternal HCMV facilitates in utero transmission of HIV and impacts the developing fetal immune system during gestation
母体 HCMV 如何促进 HIV 子宫内传播并影响妊娠期间胎儿免疫系统的发育
- 批准号:
10005430 - 财政年份:2019
- 资助金额:
$ 61.63万 - 项目类别:
How maternal HCMV facilitates in utero transmission of HIV and impacts the developing fetal immune system during gestation
母体 HCMV 如何促进 HIV 子宫内传播并影响妊娠期间胎儿免疫系统的发育
- 批准号:
10245021 - 财政年份:2019
- 资助金额:
$ 61.63万 - 项目类别:
How maternal HCMV facilitates in utero transmission of HIV and impacts the developing fetal immune system during gestation
母体 HCMV 如何促进 HIV 子宫内传播并影响妊娠期间胎儿免疫系统的发育
- 批准号:
10201228 - 财政年份:2019
- 资助金额:
$ 61.63万 - 项目类别:
Determining how macrophages regulate immunity to Zika virus infection at the maternal-fetal interface
确定巨噬细胞如何调节母胎界面对寨卡病毒感染的免疫力
- 批准号:
9882936 - 财政年份:2017
- 资助金额:
$ 61.63万 - 项目类别:
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