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Associations between maternal lifetime stressors and negative events in pregnancy and breast milk-derived extracellular vesicle microRNAs in the programming of intergenerational stress mechanisms (PRISM) pregnancy cohort.

Authors
  • Bozack, Anne K1, 2
  • Colicino, Elena2
  • Rodosthenous, Rodosthenis3
  • Bloomquist, Tessa R4
  • Baccarelli, Andrea A4
  • Wright, Robert O2
  • Wright, Rosalind J2
  • Lee, Alison G1
  • 1 Division of Pulmonary Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • 2 Department of Environmental Medicine and Public Health, New York, NY, USA.
  • 3 Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • 4 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Type
Published Article
Journal
Epigenetics
Publisher
Landes Bioscience
Publication Date
Apr 01, 2021
Volume
16
Issue
4
Pages
389–404
Identifiers
DOI: 10.1080/15592294.2020.1805677
PMID: 32777999
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20-80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |Bregression|>0.2. Enriched KEGG pathways for microRNAs associated with stress scores included fatty acid metabolism and the Hippo signaling pathway. Maternal lifetime stress and NLEs during pregnancy were both associated with detection and expression level of breast milk EV-microRNAs, although associations with microRNA profiles differed between stress measures. Further research is needed to identify biological pathways impacted by associated microRNAs and investigate relationships with child health outcomes.Abbreviations: EV: extracellular vesicle; PRISM: PRogramming of Intergenerational Stress Mechanisms pregnancy cohort; LSCR: Life Stressor Checklist-Revised survey; NLE: negative life event; CRISYS-R: Crisis in Family Systems-Revised survey; KEGG: Kyoto Encyclopaedia of Genes and Genomes; NYC: New York City; SD: standard deviation; IQR: interquartile range; Cq: relative cycle threshold values; PCA: principal component analysis.

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