Depression, perceived stress, and distress during pregnancy and EV-associated miRNA profiles in MADRES.

BACKGROUND: MicroRNA (miRNA) circulating in plasma has been proposed as biomarkers for a variety of diseases and stress measures, including depression, stress, and trauma. However, few studies have examined the relationship between stress and miRNA during pregnancy. METHODS: In this study, we examined associations between measures of stress and depression during pregnancy with miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, California. Extracellular-vesicle- (EV-) associated miRNA were isolated from maternal plasma and quantified using the Nanostring nCounter platform. Correlations for stress-associated miRNA were also calculated for 89 matching cord blood samples. RESULTS: Fifty miRNA were nominally associated with depression, perceived stress, and prenatal distress (raw p < 0.05) with 17 miRNA shared between two or more stress measures. Two miRNA (miR-150-5p and miR-148b-3p) remained marginally significant after FDR adjustment (p < 0.10). Fifteen PANTHER pathways were enriched for predicted gene targets of the 50 miRNA associated with stress. Clusters of maternal and neonate miRNA expression suggest a link between maternal and child profiles. LIMITATIONS: The study evaluated 142 miRNA and was not an exhaustive analysis of all discovered miRNA. Evaluations for stress, depression and trauma were based on self-reported instruments, rather than diagnostic tools. CONCLUSIONS: Depression and stress during pregnancy are associated with some circulating EV miRNA. Given that EV miRNA play important roles in maternal-fetal communication, this may have downstream consequences for maternal and child health, and underscore the importance of addressing mental health during pregnancy, especially in health disparities populations.

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort.

MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15-25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.