Influence of prenatal psychosocial stressors on maternal and fetal circulating miRNAs

摘要 胎儿在怀孕期间所经历的环境对健康有着深远的影响 一生的成果。婴儿生长是长期慢性疾病的一个重要危险因素， 儿童肥胖的风险。更好地了解环境可以通过哪些机制 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。这些努力可能是最需要的人口经历最大的 健康差距，环境中的逆境可能是心理社会的，物理的和化学的性质 以及这些接触可能协同作用影响健康的地方。表观遗传机制，由于 它们的发育可塑性，但长期的功能作用，已被假定为关键介质的 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，其功能是控制信使RNA（mRNA）的稳定性和翻译， 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多种细胞内信号。 生理反应包括代谢和免疫反应。由于这些角色及其固有的 由于能够影响大量的靶基因，miRNA代表了具有潜在的 广泛的后果。我们假设，除了化学应激外， 母体环境影响母体和胎儿miRNA的表达模式， 这些miRNA可以影响关键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中的全部miRNA库， 来自环境和社会压力的发育风险（MADRES）妊娠队列，重点关注 在洛杉矶县的低收入西班牙裔妇女身上。MADRES队列正在收集关于以下方面的广泛数据： 实际客观压力源（负面生活事件，过去的创伤，邻里关系障碍）和心理 对压力的反应（感知的压力和抑郁症状）沿着社会人口统计学信息， 全面了解这一人群的心理社会压力程度。这项建议 将测量已采集的妊娠早期和妊娠晚期外周血样本、脐带血样本中的miRNA 并将支持收集胎盘样本进行额外的miRNA分析。的主要目标 建议将是：1）研究产妇的心理社会压力如何影响表达模式， 在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 胎盘组织和脐带血中的miRNA表达模式与母体血清中的miRNA表达模式相似。结果 这项研究将为miRNA在介导产前基因表达影响中的作用提供证据。 环境对儿童健康的西班牙裔人口经历了显着的健康差距。

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.