# Maternal trauma, circulating microRNA in extracellular vesicles, and programming of childhood respiratory outcomes

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $829,448

## Abstract

PROJECT SUMMARY
 The developmental origins of asthma and lung growth begin in utero. A critical step in identifying
lifelong risk is characterizing exposures and mechanisms that lead to and maintain this early predisposition.
Our research team has established links between prenatal stress, including maternal lifetime trauma, and child
wheeze, asthma, and reduced lung function. We focus on traumatic experiences, which occur more commonly
in lower-income, minority women, are especially likely to lead to persistent psychophysiological alterations, and
have documented intergenerational effects. However, pathways by which maternal trauma predispose children
to respiratory disease are not well delineated. Mechanisms central to the pathophysiology of wheeze/asthma
and lung growth and development overlap and involve a cascade of events that include disrupted immune,
neuroendocrine and autonomic function as well as oxidative stress. Trauma-related alterations in these key
regulatory systems in women may persist into pregnancy and impair development of these same interrelated
systems in the fetus, increasing risk for future respiratory disease. The placenta regulates effects of the
gestational milieu on the fetus through the release of molecular signals, including microRNAs (miRNAs), small
non-coding RNAs that regulate numerous biological processes through epigenetic control of gene expression.
Placental trophoblasts actively sort miRNAs into extracellular vesicles (EVs), i.e., 0.05-1?m membrane-bound
vesicles released into maternal and fetal circulations. The secretion and content of EV-encapsulated placental
miRNAs are influenced by stress-related changes to the in utero milieu. EV-encapsulated miRNAs prime
maternal and fetal tissues via messenger RNA (mRNA) silencing that alters gene expression of large gene
sets. We leverage an established longitudinal pregnancy cohort study with measures of maternal lifetime
trauma, bio-banked maternal mid-pregnancy plasma and venous cord plasma and placental tissue collected at
birth, with ongoing respiratory phenotyping (repeated wheeze and lung function indexed by impulse
oscillometry (IOS) at age 48 months). We will investigate associations among maternal lifetime trauma, EV-
encapsulated placental miRNAs in maternal mid-pregnancy and venous cord plasma, miRNA/mRNA profiles in
placenta from normal term births ( ≥ 37 weeks), and respiratory phenotypes in children. Using a multi-stage
approach to discover and replicate placenta-specific miRNAs related to maternal trauma and child outcomes,
we may identify pathways associated with intergenerational transmission of maternal trauma and those
potentially involved in programming respiratory disease risk in children. Given the evolving understanding of
the central role of EVs in pregnancy and tissue signaling, our findings may provide a model that can be
extended to additional prenatal risk factors and other fetal disorders.

## Key facts

- **NIH application ID:** 10197782
- **Project number:** 5R01MD013310-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Alison G Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $829,448
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197782

## Citation

> US National Institutes of Health, RePORTER application 10197782, Maternal trauma, circulating microRNA in extracellular vesicles, and programming of childhood respiratory outcomes (5R01MD013310-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10197782. Licensed CC0.

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