Biocultural investigation of maternal adversity on gene expression and DNA methylation in the placenta

项目摘要/摘要 拟议的奖学金计划是一个跨学科的研究项目，综合了人类学、遗传学、 还有医学。该项目由康妮·穆利根博士(人类学系)和莫琳·凯勒博士监督。 伍德(药效学系)，由佛罗里达大学(UF)学院提供资源和支持 文科和理科、密歇根大学遗传学研究所和密歇根大学医学院。这份提案是经过精心设计的 使学员具备必要的技能，以实现她成为一名内科科学家的职业目标 在社会科学和临床医学之间架起一座桥梁。战争、性暴力和结构性 无论在美国还是国外，暴力(如贫困)仍然是一些最令人头疼的社会问题。 这些社会问题对孕妇的健康产生了负面影响，损害了双方母亲的健康。 还有新生儿。母亲的逆境与不良的新生儿结局有关，如低出生体重，这是 与成年后的一系列生理和心理后果有关。人类学使研究人员能够确定 通过一种名为民族志的方法，最具文化意义的母亲逆境经历，允许 在确定产妇不幸最突出的方面方面有更大的准确性/精确度。穆利根实验室已经 此前发现，一种基于人种学的性暴力衡量标准与 刚果民主共和国东部母子二胎新生儿出生体重和DNA甲基化信号 刚果(金)。这项提案将侧重于性暴力，原因有两个：性暴力无处不在 在美国也观察到的现象和极端母体逆境的分子特征的鉴定 可能更容易被发现。努力了解母亲压力如何影响新生儿结局的调查(例如 出生体重)主要集中在表观遗传机制上，很少关注基因表达。是这样的 研究人员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，人种学对母亲压力的测量来自于 逆境与胎盘中的表观基因组和转录特征有关。具体目标将是 母体应激与胎盘基因表达和DNA甲基化的相关性检验 以更好地了解新生儿的出生结果。中国人母子二联体的纵向队列研究 刚果民主共和国东部地区提供了一个理想的极端应激源环境，这将有助于检验这一假设。成功 这些研究的完成将加强对如何定位和实地调查孕产妇的了解 在适当的社会文化背景下促进和保护儿童健康。从这个项目中培养的技能将使 受训人员要追求她的长期目标，即调查社会差距如何在 美国境内的弱势群体。这项研究直接针对尤尼斯·肯尼迪·施莱弗NICHD 研究健康、疾病和人类胎盘发育起源的远景 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。

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.