Biocultural investigation of maternal adversity on gene expression and DNA methylation in the placenta

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PROJECT SUMMARY/ABSTRACT The proposed fellowship plan is a transdisciplinary research project integrating training in anthropology, genetics, and medicine. This project is supervised by Drs. Connie Mulligan (Dept of Anthropology) and Maureen Keller- Wood (Dept of Pharmacodynamics) with the resources and support of the University of Florida (UF) College of Liberal Arts and Sciences, the UF Genetics Institute, and the UF College of Medicine. The proposal is designed to equip the trainee with the skills necessary to attain her career goal of becoming a physician-scientist who bridges the divide between the social sciences and clinical medicine. War, sexual violence, and structural violence (e.g. poverty) continue to be some of society’s most vexing problems both in the USA and abroad. These are social problems that negatively impact the health of pregnant women to the detriment of both mothers and newborns. Maternal adversity is associated with poor newborn outcomes such as low birthweight, which is linked to a host of physical and mental consequences in adulthood. Anthropology enables researchers to identify the most culturally-salient experiences of maternal adversity through a methodology called ethnography, allowing for greater accuracy/precision in identifying the most salient aspects of maternal adversity. The Mulligan lab has previously found that an ethnographically-derived measure of sexual violence was most strongly correlated with newborn birthweight and DNA methylation signals in mother-child dyads in the eastern Democratic Republic of Congo (DRC). This proposal will focus on sexual violence for two reasons: sexual violence is a ubiquitous phenomenon also observed in the USA and identification of a molecular signature of extreme maternal adversity may be easier to detect. Investigations striving to understand how maternal stress affect newborn outcomes (e.g. birthweight) have focused primarily on epigenetic mechanisms with little attention to gene expression. Such investigations collect DNA from peripheral blood cells and neglect a tissue that is critical to newborn health: the placenta. The overarching hypothesis is that ethnographically-derived measures of maternal stress from adversity are associated with epigenomic and transcriptomic signatures in the placenta. The specific aims will test for associations between maternal stress and (1) gene expression and (2) DNA methylation in the placenta to better understand newborn birth outcomes. A longitudinal cohort study of mother-offspring dyads in the eastern DRC offers an ideal setting of extreme stressors that will facilitate testing this hypothesis. Successful completion of these studies will enhance understanding of how to situate and ground investigations of maternal and child health within the appropriate socio-cultural context. The skills cultivated from this project will enable the trainee to pursue her long-term goal of investigating how social disparities become health disparities in disadvantage populations within the USA. This research directly targets the Eunice Kennedy Shriver NICHD vision for investigations into the Developmental Origins of Health and Disease and The Human Placenta Project’s research objective to better understand contributions of placental development to health and disease.