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
• 负责人: Rana Chakraborty
• 金额: $ 62.85万
• 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/10523426
• 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; 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/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; 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.

项目概要 自建国之初，结构性种族主义和歧视（SRD）一直是美国的历史遗产。 1619 年非洲人口被奴役，进入种族隔离时代（“吉姆·克劳”），该时代以内政和 隐藏在视线之外的是种族创伤的生物学影响。 认识到 SRD 是使非裔美国人健康方面的种族差距长期存在的一个重要机制。 特别是，研究记录了 SRD 对不良妊娠结局的影响，包括更高的发生率 非裔美国 (AA) 妇女的早产率和黑人母亲的死亡率较高 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。 经济状况和教育；并已被证明可能通过表观遗传持续代际 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。 AA 女性中母胎界面处明显的表观遗传修饰与改变有关 研究表明，胎盘和发育中的胎儿中的免疫细胞发育、激活和信号传导。 越来越多的证据表明，胎盘可能是母体跨代表观遗传的门户。 表明子宫内表观遗传变化的影响不仅仅影响母亲和孩子，而且 通过成年期传递到种系，从而损害后代的胎盘。 表观遗传学与宫内生长受限、早产和先兆子痫有关，这些都是 研究表明种族与胎盘炎症有关。 此外，跨代创伤造成的高压力与慢性疾病有关。 然而，胎盘炎症和不良妊娠结局的生物学特性。 妊娠结局的差异仍然未知。我们勇敢地面对与 SRD 相关的创伤的传播。 跨代并表现出促进炎症和先天性的表观遗传模式 提出了胎盘和胎儿免疫功能障碍的三个具体目标：1）评估负担。 SRD 对 AA 孕妇的母亲压力、全身炎症和表观遗传特征的影响 2) 对 AA 和 CA 胎盘进行比较转录、表观遗传学和免疫学分析 孕妇以确定与 SRD 相关压力相关的特定变化；以及 3) 在子宫内进行调查； AA 新生儿免疫反应的编程和特定表观遗传特征的遗传 暴露于母体 SRD 相关应激下的 SRD 对胎盘表观遗传改变的生物学影响。 可能会增加婴儿期和儿童期早产和不良后果的可能性。 这些研究可能为未来解决此类健康风险的干预措施提供信息，并可以促进健康和福祉。 属于高危母婴对。