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.

项目概要/摘要 拟议的研究金计划是一个跨学科研究项目，整合了人类学、遗传学、 和医学。该项目由博士监督。康妮·穆里根（人类学系）和莫林·凯勒- Wood（药效学系）在佛罗里达大学 (UF) 学院的资源和支持下 文理学院、佛罗里达大学遗传学研究所和佛罗里达大学医学院。该提案设计 使受训者具备必要的技能，以实现成为一名医师科学家的职业目标 弥合了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）仍然是美国和国外社会最棘手的问题。 这些社会问题会对孕妇的健康产生负面影响，从而损害母亲双方的利益 和新生儿。母亲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心后果有关。人类学使研究人员能够识别 通过一种称为民族志的方法，研究母亲逆境中最具有文化意义的经历，使 提高识别孕产妇逆境最显着方面的准确性/精确度。 Mulligan 实验室有 先前发现，从人种学角度得出的性暴力衡量标准与 民主共和国东部母子二人组的新生儿出生体重和 DNA 甲基化信号 刚果（金）。该提案将重点关注性暴力，原因有两个： 性暴力是一种普遍存在的现象。 美国也观察到这种现象，并鉴定了极端母亲逆境的分子特征 可能更容易检测到。旨在了解母亲压力如何影响新生儿结局的调查（例如 出生体重）主要关注表观遗传机制，很少关注基因表达。这样的 研究从外周血细胞收集 DNA，却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测量方法 逆境与胎盘的表观基因组和转录组特征有关。具体目标将 测试母体压力与胎盘中 (1) 基因表达和 (2) DNA 甲基化之间的关联 更好地了解新生儿的出生结果。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理想的极端压力环境，这将有助于检验这一假设。成功的 完成这些研究将加深对如何对孕产妇进行定位和实地调查的理解 和适当社会文化背景下的儿童健康。通过该项目培养的技能将使 学员追求她的长期目标，即调查社会差异如何成为健康差异 美国境内的弱势群体。这项研究直接针对尤尼斯·肯尼迪·施赖弗 (Eunice Kennedy Shriver) NICHD 研究健康和疾病的发育起源以及人类胎盘的愿景 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。