Influence of prenatal psychosocial stressors on maternal and fetal circulating miRNAs

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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.