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，母亲的健康会影响孩子的健康。此外，众所周知，母亲怀孕时的经历（即产生本质的经历）会影响孩子的健康，无论是在他们的出生和整个生命时都会影响孩子的健康。未知的是如何将有关母亲健康的信息传递给发育中的胎儿，此外，这些信息如何影响儿童的健康。该项目是第一个测试极端环境或社会心理压力源可能会导致健康结果改变的可能性之一，这可能会以一种可遗传的多代方式。具体而言，研究人员将确定表观遗传变化是否是基因表达的遗传变化，不会影响潜在的DNA序列，将压力和创伤对母亲的影响转化为新生儿的健康结果的改变。调查人员正在刚果民主共和国工作，那里的内战和将强奸用作武器为地球上妇女创造了最紧张和最创伤的环境之一。将通过对母亲的广泛访谈来制定与文化相关的压力措施，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进行测试。尖端的DNA测序技术将用于在独特的母纽伯恩样品集上生成有史以来最大的表观遗传数据集。研究人员将寻找孕产妇应力与新生儿健康结果之间的联系，这些结局是由基因表达的表观遗传改变介导的。在其他实验室进行的正在进行的研究表明，有可能设计治疗以逆转压力暴露而进行的表观遗传变化，这对我们解决社会一些最征税问题的能力具有深远的影响。拟议的研究是第一个研究人类中表观遗传改变（基因表达的变化（基因表达的变化）），这可能是对母亲周日应激和对母亲的创伤的可能反应，从而导致后代的健康结果改变。暴力和压力暴露会导致新生儿健康结果的变化，大概是通过基因表达的变化而变化，并且与全球公共卫生问题直接相关。从最广泛的角度来看，这项提案和类似的研究对我们的理解和试图改善社会最令人烦恼的问题的尝试具有深远的影响，包括暴力，虐待和贫困的多代循环。拟议的研究将提高我们对人类压力与健康之间的联系的理解，并对美国与压力相关的疾病的普遍性增加具有广泛的影响。该项目具有广泛的跨学科观点，该观点将人类遗传学，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融合在一起。此外，已经与佛罗里达大学的科学思维和教育伙伴关系合作制定了一项研究生培训计划，人类学的学生将充当生产助手，以开发沟通材料，以向公众传播研究结果。学生将接受新闻写作，打印布局和视频制作的培训，以便他们更好地将其研究与非科学受众传达。