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

母体逆境对胎盘基因表达和 DNA 甲基化影响的生物文化研究

基本信息

批准号：
10627749
负责人：
Chu Hsiao
金额：
$ 5.23万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-16 至 2024-05-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10627749
关键词：
Address Adult Affect Animals Anthropology Arts Attention Birth Birth Weight Blood Cells Blood Pressure Candidate Disease Gene Child Chronic Disease Clinical Medicine Collaborations Complex DNA DNA Methylation Democratic Republic of the Congo Development Discipline Disease Disparity population Distress Epigenetic Process Ethnography Fellowship Fetal Growth Retardation Fetus Florida Functional disorder Future Gene Expression Gene Expression Profile Genes Genetic Genetic Markers Glucocorticoid Receptor Goals Health Heritability Human Hypertension Inequality Insulin Resistance Investigation Link Literature Longitudinal cohort study Low Birth Weight Infant Maternal and Child Health Measures Medicine Mental Health Methodology Molecular Molecular Profiling Mothers NR3C1 gene National Institute of Child Health and Human Development Newborn Infant Outcome Participant Pathology Pathway interactions Patients Perinatal Pharmacodynamics Phenotype Physicians Placenta Placentation Play Poverty Pregnant Women Prevalence Probability Psyche structure Psychosocial Stress Research Research Personnel Research Project Grants Resources Risk Role Science Scientist Signal Transduction Social Environment Social Problems Social Sciences Societies Stress Testing Tissues Training Universities Variant Violence Vision War Woman Wood material adverse pregnancy outcome biomarker identification cardiovascular health career college design disorder risk early life adversity epigenome epigenomics experience gene environment interaction genetic variant health disparity improved insight intergenerational maternal stress men neglect neonatal health novel offspring physical conditioning reproductive outcome sexual violence skills social social culture social disparities stressor transcriptome transcriptomics transmission process

项目摘要

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.

项目总结/文摘

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Peripartum women's perspectives on research study participation in the OneFlorida Clinical Research Consortium during COVID-19 pandemic.

果皮妇女对研究研究参与的研究观点，在Covid-19-19大流行期间。

DOI：
10.1017/cts.2022.476
发表时间：
2023
期刊：
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
影响因子：
2.6
作者：
Xu, Ke;Hsiao, Chu J. J.;Ballard, Hailey;Chachad, Nisha;Reeder, Callie F. F.;Shenkman, Elizabeth A. A.;Flood-Grady, Elizabeth;Louis-Jacques, Adetola F. F.;Smith, Erica L. L.;Thompson, Lindsay A. A.;Krieger, Janice;Francois, Magda;Lemas, Dominick J. J.
通讯作者：
Lemas, Dominick J. J.

Prenatal maternal stress is associated with site-specific and age acceleration changes in maternal and newborn DNA methylation.