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: 10710037
• 负责人: Rana Chakraborty
• 金额: $ 61.63万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10710037
• 关键词: Accounting; Address; Adult; African; African American; African American population; African ancestry; Awareness; Biological; Biological Markers; Black race; Cells; Child; Childhood; Chromatin Structure; Chronic; Civil Rights; Crows; Development; Discrimination; Disparity; Education; Environment; Epigenetic Process; Exposure to; Fetal Development; Fetal Growth Retardation; Fetus; Future; Gene Expression; Generations; Genetic Transcription; Genomic DNA; Health; Health Promotion; Immune; Immune System Diseases; Immune response; Immunity; Immunologics; Infant; Infant Health; Infant Mortality; Inflammation; Inflammation Mediators; Inflammatory; Inheritance Patterns; Inherited; Intervention; Link; Maternal Health; Maternal-Fetal Exchange; Modification; Mononuclear; Mothers; Pathology; Pattern; Personal Satisfaction; Phenotype; Physiological; Placenta; Placentation; Population; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Property; Race; Risk; Shapes; Signal Transduction; Socioeconomic Status; Standardization; Stress; Structural Racism; Surveys; Tissues; Training; Trauma; Umbilical Cord Blood; United States; Vision; Voting Right; Woman; adverse outcome; bisulfite sequencing; caucasian American; cohort; comparative; cytokine; digital; experience; fetal; fetal immunity; genetic signature; genome-wide; genomic platform; health disparity; immune activation; immunoregulation; in utero; infancy; infant morbidity; infant morbidity/mortality; inflammatory marker; maternal stress; mortality; multiple omics; nano-string; neonate; perceived stress; racial disparity; response; systemic inflammatory response; transcriptome; transcriptome sequencing; transcriptomics; transgenerational epigenetic inheritance; transmission process; whole genome

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）从一开始就一直是美国的历史遗产 1619年，非洲人口奴役为种族隔离时代（“吉姆·克劳”），该时代以公民和公民结束 投票权法案。隐藏在平淡无奇的是种族创伤的生物学影响。越来越多 意识到SRD是一种显着的机制，它使非洲裔美国人的健康差距永久存在。在 特别是，研究记录了SRD对负妊娠结果的影响，包括较高的率 非裔美国人（AA）妇女的早产以及黑人母亲的死亡率较高 婴儿。即使考虑到社会 - 经济状况和教育；并已证明通过表观遗传持续存在变革 影响。在这项研究中，我们试图研究种族和变革性SRD相关创伤的影响 在AA妇女进行的，在母亲界面的不同表观遗传修饰中，与变化有关 免疫细胞的发育，活化和信号传导和发育的胎儿。研究表明 斑点可以是母体变换表观遗传遗传的门户。越来越多的证据 表明在子宫表观遗传变化中的影响超出了母亲和孩子的影响，并且是 通过成年后，进入种系，确定成功的世代。干扰的斑点 表观遗传学与泌尿内生长限制，早产和胎儿前的遗传学有关，这是 AA中婴儿死亡的驱动因素。研究表明，种族与局部炎症有关 病理。此外，由于转化创伤引起的高压力率与慢性有关 plopeta和妊娠结局不良的炎症。但是，形状的生物学特性 怀孕结局的差异仍然未知。我们假设SRD相关的创伤已传播 跨越几代人和表观遗传遗传模式，促进炎症和先天 胎盘和胎儿的免疫功能障碍。提出了三个具体目标：1）评估伯恩 AA孕妇的孕产妇压力，全身感染和表观遗传学特征的SRD； 2） 从AA和CA进行胎盘的比较转录，表观遗传和免疫学分析 孕妇确定与SRD相关应力相关的特定变化； 3）在子宫里进行调查 免疫反应的编程和AA新生儿中特定表观遗传特征的遗传 暴露于母亲SRD相关的应力。 SRD对plapeta表观遗传改变的生物学影响 可能有助于增加早产和婴儿期不良后果的脆弱性。 这些研究可能会为未来的干预措施提供信息，以应对这种健康风险，并可以促进健康和健康 是处于危险的母亲对。