Epigenetic alterations and stress among new mothers and neonates in the Democratic Republic of Congo: A biocultural investigation of the intergenerational effects of war

刚果民主共和国新妈妈和新生儿的表观遗传改变和压力：战争代际影响的生物文化调查

基本信息

批准号：
1231264
负责人：
Connie Mulligan
金额：
$ 35.33万
依托单位：
University of Florida
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1231264&HistoricalAwards=false
关键词：
Epigenetic alterations stress among new

项目摘要

It has been known for decades that a mother's health impacts the health of her children. Moreover, it is known that a mother's experiences while she is pregnant (i.e., peri-natal experiences) affect her children's health, both when they are born and throughout their lives. What is unknown is how information about the mother's health is transmitted to the developing fetus and, furthermore, how this information impacts children's health throughout their lives. This project is one of the first to test the possibility that extreme environmental or psychosocial stressors may result in altered health outcomes, possibly in a heritable, multigenerational manner. Specifically, the investigators will determine if epigenetic changes, which are inherited changes in gene expression that do not affect the underlying DNA sequence, translate the impact of stress and trauma to mothers into altered health outcomes in newborns. The investigators are working in the Democratic Republic of Congo, where ongoing civil war and the use of rape as a weapon has created one of the most stressful and traumatic environments for women on the planet. Culturally relevant measures of stress will be developed through extensive interviews with mothers and these data will be tested against patterns of epigenetic variation detected in DNA samples collected from mothers and their newborns. Cutting-edge DNA sequencing techniques will be used to generate the largest epigenetic dataset ever on a unique set of mother-newborn samples. Investigators will look for a connection between maternal stress and newborn health outcome that is mediated by epigenetic alterations in gene expression. Ongoing research in other laboratories indicate that it may be possible to devise treatment to reverse epigenetic alterations made in response to stress exposures, which has profound implications for our ability to address some of society's most taxing problems. The proposed study is the first to investigate epigenetic alterations (changes in gene expression that do not change the underlying DNA sequence) in humans as a possible response to peri-natal stress and trauma to mothers that results in altered health outcomes in offspring. The idea that violence and stress exposure can create changes in newborn health outcome, presumably through changes in gene expression, has immediate relevance to global public health issues. Seen from the broadest perspective, this proposal and similar research has profound implications for our understanding and attempts to ameliorate society's most vexing problems, including multigenerational cycles of violence, abuse and poverty. The proposed research will improve our understanding of the link between stress and health in humans and has broad implications for the increasing prevalence of stress-related disorders in the United States. The project takes a broad, interdisciplinary perspective that integrates human genetics, cultural anthropology and sociology, biology and psychology, as well as political realities and public health policy. Furthermore, a graduate training program has been developed in collaboration with the University of Florida's Scientific Thinking and Education Partnership in which anthropology students will act as production assistants to develop communication materials to disseminate research results to the general public. Students will receive training in news writing, print layout, and video production to prepare them to better communicate their research to a non-science audience.

几十年来，人们都知道母亲的健康会影响孩子的健康。此外，众所周知，母亲怀孕期间的经历（即围产期经历）会影响孩子出生时和一生的健康。目前尚不清楚的是，有关母亲健康的信息如何传递给发育中的胎儿，以及这些信息如何影响儿童一生的健康。该项目是第一个测试极端环境或心理社会压力可能导致健康结果改变的可能性的项目之一，可能以遗传的、多代的方式。具体来说，研究人员将确定表观遗传变化（即不影响潜在 DNA 序列的基因表达的遗传变化）是否会将压力和创伤对母亲的影响转化为新生儿健康结果的改变。调查人员正在刚果民主共和国开展工作，该国持续的内战和以强奸为武器的行为给妇女带来了地球上压力最大、创伤最大的环境之一。将通过对母亲的广泛访谈来制定与文化相关的压力测量方法，并将根据从母亲及其新生儿收集的 DNA 样本中检测到的表观遗传变异模式对这些数据进行测试。尖端的 DNA 测序技术将用于在一组独特的母婴样本上生成有史以来最大的表观遗传数据集。研究人员将寻找母亲压力与新生儿健康结果之间的联系，这种联系是由基因表达的表观遗传改变介导的。其他实验室正在进行的研究表明，有可能设计出治疗方法来逆转因压力暴露而发生的表观遗传改变，这对我们解决一些社会最棘手问题的能力具有深远的影响。这项拟议的研究是第一个调查人类表观遗传改变（不改变潜在 DNA 序列的基因表达变化）作为对围产期压力和母亲创伤的可能反应，从而导致后代健康结果改变的情况。暴力和压力暴露可以通过基因表达的变化改变新生儿的健康结果，这一观点与全球公共卫生问题直接相关。从最广泛的角度来看，这项提议和类似的研究对于我们理解和尝试改善社会最棘手的问题（包括暴力、虐待和贫困的多代循环）具有深远的影响。拟议的研究将增进我们对人类压力与健康之间联系的理解，并对美国日益流行的压力相关疾病产生广泛影响。该项目采用广泛的跨学科视角，整合了人类遗传学、文化人类学和社会学、生物学和心理学，以及政治现实和公共卫生政策。此外，与佛罗里达大学的科学思维和教育伙伴关系合作制定了研究生培训计划，其中人类学学生将担任制作助理，开发传播材料，向公众传播研究成果。学生将接受新闻写作、印刷版面和视频制作方面的培训，以帮助他们更好地向非科学受众传达他们的研究成果。