The Impact of Transgenerational Racial Trauma on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy. Comparisons Between Caucasian and African American Populations

项目摘要 结构性种族主义和歧视（SRD）从2000年开始就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，包括更高的发生率 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。即使在考虑了社会因素后，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。

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.