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