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.

项目摘要/摘要 拟议的奖学金计划是一个跨学科研究项目，该项目整合了人类学，遗传学， 和医学。该项目由Drs监督。康妮·穆里根（Connie Mulligan）（人类学部）和莫琳·凯勒（Maureen Keller） 佛罗里达大学（UF）学院的资源和支持的木材（药效学系） 文科和科学，UF遗传学研究所和UF医学院。该提案的设计 为学员配备实现自己的职业目标所必需的技能，成为一个身体科学家 桥接社会科学与临床医学之间的鸿沟。战争，性暴力和结构性 在美国和国外，暴力（例如贫困）仍然是社会上最烦人的问题。 这些是社会问题，对孕妇的健康对两位母亲的确定产生负面影响 和新生儿。产妇广告与新生儿不良结果（例如低出生体重）有关 与成年后的许多身心后果有关。人类学使研究人员能够识别 孕产妇逆境的最文化偏见的经历通过一种称为人种志的方法，允许 为了更高的准确性/精确度，以识别孕产妇广告的最显着方面。 Mulligan实验室有 以前发现，民族志衍生的性暴力的衡量与 东部民主共和国的母子二元组中的新生出生体重和DNA甲基化信号 刚果（DRC）。该提议将重点关注性暴力，原因有两个：性暴力无处不在 现象在美国也观察到了极端孕产妇广告的分子标志的识别 可能更容易检测到。努力了解基质应力如何影响新生儿结果的调查（例如 生日）主要集中在表观遗传机制上，而对基因表达的关注很少。 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： placeta。总体假设是民族志衍生的孕产妇压力的措施 逆境与plapeta中的表观基因组和转录组特征有关。具体目标将 测试MATER胁迫与（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。一项纵向队列研究在 东刚果民主共和国提供了极端压力源的理想设置，可以促进检验这一假设。成功的 这些研究的完成将增强人们对孕产妇的位置和地面研究的理解 和儿童健康在适当的社会文化背景下。该项目所培养的技能将使 受训者追求她的长期目标，即调查社会差异如何成为健康差异 美国境内的劣势人口。这项研究直接针对Eunice Kennedy Shriver Nichd 对健康和疾病的发育起源和人类plapeta进行调查的愿景 项目的研究目标是更好地了解占地面积对健康和疾病的贡献。