Influence of prenatal psychosocial stressors on maternal and fetal circulating miRNAs

摘要 发育中的胎儿在怀孕期间所经历的环境可能会对健康产生深远的影响 一生的结果。婴儿的生长发育是长期慢性疾病的重要风险因素，尤其是 童年后期患肥胖症的风险。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进风险评估，并为新的 预防方法。这些努力可能是最需要的人群中经历最大的 健康差异，环境中的逆境本质上可以是心理、物理和化学方面的 这些暴露可能会协同作用影响健康。表观遗传机制，由于 他们的发育可塑性但长期的功能作用，已被认为是关键的中介。 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 蛋白质的含量。越来越多的证据表明，miRNA可以作为细胞间信号来调节各种不同的 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 能够影响大量的靶基因，miRNA代表着潜在的 广泛的后果。我们假设，除了化学应激源外，心理社会因素在 母体环境影响母体和胎儿miRNA的表达模式 这些miRNA可能会影响关键的新生儿和早期生命健康结果。我们将检验这一假设 使用最先进的技术表征母亲和母亲中miRNA的全部谱系 环境和社会应激源(MADRES)妊娠队列的发育风险，重点是 关于洛杉矶县的低收入西班牙裔女性。Madres的队列正在收集大量关于 实际的客观应激源(负性生活事件、既往创伤、邻里关系紊乱)和心理 对压力的反应(感觉到的压力和抑郁症状)以及社会人口信息 全面了解这一人群经历的心理社会压力的程度。这项建议 将检测已采集的妊娠早期和晚期外周血样本、脐带血样本中的miRNA 在出生时，将支持收集胎盘样本以进行更多miRNA分析的努力。的主要目标是 该提案将1)检查母亲的心理社会压力如何影响 孕妇血液中的miRNA，2)描绘了母亲循环中miRNA对新生儿的影响 健康结果，包括出生体重和小于妊娠的出生，以及3)检查 MiRNA在胎盘组织和脐带血中的表达模式与母体血清中的表达模式。结果： 这项研究将为miRNA在调节产前效应中所起的作用提供证据。 在经历了严重健康差距的西班牙裔人口中，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.