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

• 批准号: 10397565
• 负责人: Chu Hsiao
• 金额: $ 5.41万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 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/10397565
• 关键词: Address; Adult; Affect; Animals; Anthropology; Arts; Attention; Biological Markers; Birth; Blood Cells; Blood Pressure; Candidate Disease Gene; Child; Chronic Disease; Clinical Medicine; Complex; DNA; DNA Methylation; Democratic Republic of the Congo; Development; Discipline; Disease; Distress; Epigenetic Process; Ethnography; Fellowship; Fetal Growth Retardation; Fetus; Florida; Functional disorder; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Markers; Genetics and Medicine; Goals; Health; Heritability; Human; Hypertension; Inequality; Institutes; 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; 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; Supervision; Testing; Tissues; Training; Universities; Variant; Violence; Vision; War; Woman; Wood material; adverse pregnancy outcome; cardiovascular health; career; college; design; disadvantaged population; disorder risk; early life adversity; epigenome; epigenomics; experience; gene environment interaction; genetic variant; glucocorticoid receptor alpha; 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

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/摘要 拟议的研究金计划是一个跨学科的研究项目，将人类学、遗传学、 和医药该项目由Connie Mulligan博士（人类学系）和Maureen Keller博士监督- 伍德（药效学系）与佛罗里达大学（UF）的资源和支持， 文科和理科，UF遗传学研究所，和医学的UF学院。该提案旨在 使受训者具备必要的技能，以实现她成为一名医生-科学家的职业目标， 弥合社会科学和临床医学之间的鸿沟。战争、性暴力和结构性暴力 暴力（例如贫困）仍然是美国和国外最令人烦恼的社会问题。 这些社会问题对孕妇的健康产生不利影响，对母亲双方都不利 和新生儿。产妇逆境与新生儿不良结局有关，例如低出生体重，这是 与成年后的一系列身体和精神后果有关。人类学使研究人员能够识别 通过一种叫做民族志的方法， 以更准确/精确地确定母亲逆境的最突出方面。穆里根实验室 先前发现，一个民族志衍生的性暴力措施是最密切相关的， 刚果民主共和国东部新生儿出生体重和母子二人组DNA甲基化信号 刚果（刚果民主共和国）。这项提案将重点放在性暴力上，原因有二：性暴力是一种普遍存在的 在美国也观察到这种现象，并确定了极端母亲逆境的分子特征 可能更容易被发现。努力了解产妇压力如何影响新生儿结局的调查（例如， 出生体重）主要集中在表观遗传机制，很少关注基因表达。等 研究从外周血细胞中收集DNA，忽略了对新生儿健康至关重要的组织： 胎盘最重要的假设是，从人种学角度得出的母亲压力的测量结果， 逆境与胎盘中的表观基因组和转录组标记相关。具体目标将 测试母体压力与（1）基因表达和（2）胎盘中DNA甲基化之间的关联 以更好地了解新生儿出生结果。中国汉族人群母子二人组的纵向队列研究 刚果民主共和国东部提供了一个极端压力的理想环境，将有助于测试这一假设。成功 这些研究的完成将提高对如何对孕产妇死亡进行调查和实地调查的认识。 在适当的社会文化背景下促进儿童健康。从这个项目中培养的技能将使 培训生追求她的长期目标，调查社会差距如何成为健康差距， 美国境内的弱势群体。这项研究直接针对尤妮斯肯尼迪施莱佛NICHD 健康和疾病的发展起源和人类胎盘的调查愿景 该项目的研究目标是更好地了解胎盘发育对健康和疾病的贡献。