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.

项目总结