A biocultural investigation of epigenetics, gene expression and the intergenerational effects of stress in mothers and neonates

该项目将研究母亲在怀孕期间经历极端压力的母婴对样本中母亲压力、表观遗传标记和婴儿结局之间的关系。该研究的目的是更好地了解表观遗传机制如何将一代人的压力与基因表达的变化和下一代的晚年结果联系起来。压力（包括社会心理压力）可能与后代以后生活结果的变化在生理上相关，这一观点是许多生长、发育、适应和可塑性人类学模型的核心。该研究结果还可能为了解美国日益流行的压力相关疾病提供信息。该项目将支持正在进行的国际研究合作以及生物、文化和医学人类学方面的综合研究生培训，为来自 STEM 领域代表性不足的群体的学生提供支持。刚果民主共和国 (DRC) 是当今压力最大的环境之一，战争和战后冲突已对该国造成了 20 多年的蹂躏。该项目将研究 DNA 甲基化和基因表达在将母亲样本中的暴力和压力经历转化为这些母亲及其后代的福祉结果改变方面的作用。因此，该项目将增进我们对人类表型可塑性的理解，这是人类学、生物文化研究的中心主题。 所提出的生物文化方法整合了复杂的人种学、表观基因组、转录组和激素数据；已经收集了 100 对母婴的大量生物样本、孕产妇压力暴露和新生儿/产妇结局。将对生物样本进行 DNA 甲基化 (Illumina MmethylationEPIC BeadChip)、基因表达（Agilent SurePrint G3 人类基因表达阵列）和基于皮质醇的压力测量（ELISA 和 LC-MS）的检测。将使用多元回归分析来测试母体压力、DNA 甲基化、基因表达和新生儿/母体结局之间的关联，以更好地了解压力适应性反应背后的生物和分子机制。该项目将重点关注参与应激过程的基因，例如 HPA 轴基因，以及整个基因组，以测试应激对全基因组的影响。

This project will investigate relationships among maternal stress, epigenetic markers, and infant outcomes in a sample of mother-infant pairs in which the mothers experienced extreme stress during pregnancy. The goal of the research is to better understand how epigenetic mechanisms may link stress in one generation and changes in gene expression and later-life outcomes in the next generation. The idea that stress, including psychosocial stress, may be related physiologically to changes in an offspring's outcomes later in life is central to many anthropological models of growth, development, adaptation and plasticity. The research findings also will be potentially informative for understanding the increasing prevalence of stress-related disorders in the United States. This project will support ongoing international research collaborations and integrative graduate training in biological, cultural, and medical anthropology for students from groups underrepresented in STEM fields. One of the most stressful environments today is found in the Democratic Republic of Congo (DRC) where war and post-war conflict has ravaged the country for over 20 years. This project will investigate the role of DNA methylation and gene expression in translating experiences of violence and stress in a sample of mothers into altered well-being outcomes for those mothers and their offspring. The project will therefore advance our understanding of human phenotypic plasticity, a central theme in anthropological, biocultural research. The proposed biocultural approach integrates sophisticated ethnographic, epigenomic, transcriptomic, and hormonal data; a wealth of biological samples, maternal stress exposures and neonate/maternal outcomes have already been collected for 100 mother-infant pairs. The biological samples will be assayed for DNA methylation (Illumina MethylationEPIC BeadChip), gene expression (Agilent SurePrint G3 Human Gene Expression array), and cortisol-based stress measures (ELISA and LC-MS). Associations among maternal stress, DNA methylation, gene expression and neonate/maternal outcomes will be tested using multiple regression analyses, to better understand the biological and molecular mechanisms that underlie adaptive responses to stress. The project will focus on genes involved in the stress process, e.g., HPA axis genes, as well as the entire genome to test for genome-wide effects of stress.