Influence of prenatal psychosocial stressors on maternal and fetal circulating miRNAs

摘要 胎儿在妊娠期间所经历的环境会对健康产生深远的影响 终生的结果。婴儿生长是长期慢性疾病的重要危险因素，特别是 儿童后期肥胖的风险。更好地了解环境可以通过的机制 计划后代肥胖风险可能有助于改善风险评估并提供新的机会 预防方法。这些努力对于经历最严重的人群来说可能是最需要的 健康差异，环境中的逆境本质上可能是社会心理、物理和化学方面的 以及这些暴露可能协同作用影响健康。表观遗传机制，由于 它们的发育可塑性和长期功能作用，已被认为是 环境对儿童健康的影响。非编码 RNA，特别是 microRNA (miRNA)，代表 一种表观遗传机制，可控制信使 RNA (mRNA) 和翻译的稳定性 蛋白质。越来越多的证据表明 miRNA 可以作为细胞间信号来调节各种 生理反应包括新陈代谢和免疫反应。由于这些角色及其固有的 miRNA 具有影响大量靶基因的能力，代表了具有潜力的基本调节因子 广泛的后果。我们假设，除了化学应激源之外，心理社会因素 母体环境影响母体和胎儿 miRNA 的表达模式，并且 这些 miRNA 可以影响重要的新生儿和早期生命健康结果。我们将检验这个假设 使用最先进的技术来表征母体和母体中 miRNA 的完整库。 环境和社会压力源的发育风险 (MADRES) 妊娠队列，重点关注 洛杉矶县低收入西班牙裔妇女。 MADRES 队列正在收集大量数据 实际客观压力源（负面生活事件、过去的创伤、邻里关系混乱）和心理压力 对压力的反应（感知到的压力和抑郁症状）以及社会人口统计信息 全面了解该人群所经历的社会心理压力的程度。这个提议 将测量已收集的第一和第三个月外周血样本、脐带血样本中的 miRNA 出生时，并将支持收集胎盘样本以进行额外 miRNA 分析的工作。主要目标 该提案将是 1) 检查母亲社会心理压力如何影响母亲的表达模式 怀孕期间母体血液中的 miRNA，2) 描述母体循环 miRNA 如何影响新生儿 健康结果，包括出生体重和小于胎龄儿，以及 3) 检查两者之间的关系 胎盘组织和脐带血中 miRNA 与母体血清中 miRNA 的表达模式。结果 这项研究将为 miRNA 在介导产前影响中发挥的作用提供证据。 西班牙裔人口中存在显着的健康差异，环境对儿童健康的影响。

ABSTRACT The environment experienced by a developing fetus during gestation can have profound impacts on health outcomes throughout life. Infant growth is a significant risk factor for long-term chronic disease, particularly later childhood risk for obesity. A better understanding of the mechanisms through which the environment can program offspring obesity risk may help to improve risk assessment as well as provide opportunities for novel prevention approaches. These efforts may be most needed amongst populations experiencing the greatest health disparities, where adversities in the environment can be psychosocial, physical, and chemical in nature and where these exposures may be acting synergistically to impact health. Epigenetic mechanisms, due to their developmental plasticity but long-term functional role, have been posited as critical mediators of the environment’s impact on children’s health. Non-coding RNA, and particularly, microRNA (miRNA), represent one epigenetic mechanism that functions to control the stability of messenger RNA (mRNA) and the translation of proteins. There is growing evidence that miRNA can act as an inter-cellular signal to modulate various physiologic responses including metabolism and immune response. Due to these roles and their inherent ability to effect large numbers of target genes, miRNA represent fundamental regulators with the potential for wide-ranging consequences. We hypothesize that psychosocial, in addition to chemical stressors, in the maternal environment impact the pattern of expression of maternal and fetal miRNA and that the expression of these miRNA can impact critical newborn and early life health outcomes. We will examine this hypothesis using state-of-the-art technologies to characterize the full repertoire of miRNA in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which focuses on low income Hispanic women in Los Angeles county. The MADRES cohort is collecting extensive data on actual objective stressors (negative life events, past trauma, neighborhood disorder) and the psychological response to stress (perceived stress and depression symptoms) along with socio-demographic information to comprehensively understand the extent of psychosocial stress experienced in this population. This proposal will measure miRNA in already collected peripheral blood samples 1st and 3rd trimesters, cord blood samples at birth, and will support the effort to collect placental samples for additional miRNA analysis. The main aims of the proposal will be to 1) examine how maternal psychosocial stress impacts the pattern of expression of miRNA in maternal blood during pregnancy, 2) delineate how maternal circulating miRNA impact newborn health outcomes including birth weight and small-for-gestational birth, and 3) examine the relationship between patterns of expression of miRNA in placental tissue and in cord blood to those in maternal serum. Results of this study will provide evidence for the role that miRNA play in mediating the effects of the prenatal environment on children’s health within a Hispanic population experiencing significant health disparities.