# Molecular Antecedents of Miscarriage

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $733,193

## Abstract

Miscarriage - defined as pregnancy loss prior to 20 weeks of gestation - is the most common pregnancy
complication, affecting 10-20% of clinically recognized pregnancies. While advances have been made in
noninvasive prenatal diagnosis of chromosomal abnormalities leading to pregnancy loss, the pathophysiology
and environmental causes of chromosomally normal losses – the bulk of miscarriages occurring after the 6th
gestation week – remain largely unexplained. We hypothesize that microRNAs serve as a physiologic “glue” for
common pathways predicting loss of chromosomally normal pregnancies. MicroRNAs are non-coding RNAs that
negatively regulate gene expression by inducing translational inhibition or mRNA degradation. Because of their
remarkable stability in the circulation and their ability to report on or regulate cellular and tissue phenotypes in
distal anatomic sites, they present an attractive novel target for mechanistic and diagnostic biomarker research.
miRNA expression is controlled by a variety of exposures not yet deciphered in pregnant women. In our global
transcriptomics pilot, we discovered circulating miRNAs that are differentially expressed in typical pregnancy
compared to pre-conception and to pregnancy in women who later miscarry. This application responds to a
strategic priority identified by NICHD. We leverage the rich dataset of demographic, socio-economic and
maternal health data and the biospecimen archive of three large early pregnancy cohorts (>8000 enrolled
participants) and align them with technological resources offered under GLP practice by four participating
laboratories. Drawing on the largest sample of miscarriages ever examined in relation to prospectively obtained
biological data (250 chromosomally normal miscarriages) and building on the technological resources offered
under GLP practice by four participating laboratories, we will: Aim 1: Identify prodromal molecular signatures of
miscarriage, in pre-miscarriage maternal blood, free of common chromosomal defects: 1.1 identify miRNAs and
miRNA-targeted pathways dysregulated in such miscarriages and 1.2 test associations with gestational age at
miscarriage;1.3 determine whether hypothesis-driven biomarkers of deficient endometrial function, inflammation,
oxidative stress, hormonal imbalance, and coagulopathy/hemostatic injury are associated with such
miscarriages; and 1.4. whether they mediate an association between miRNA and miscarriage. Aim 2: Apply
omics in maternal urine to identify environmental exposures associated with miscarriages free of common
chromosomal defects; and Aim 3: Explore whether miRNA antecedents mediate an association between
miscarriage and elements of the maternal exposome, including chemicals, and socioeconomic and health-
related stressors. The proposed research will generate high-dimensional data for the research community and
open the door to novel predictive models of the adverse effects of chemical exposures in pregnant women. The
study...

## Key facts

- **NIH application ID:** 10873307
- **Project number:** 5R01HD105358-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** RAINA N. FICHOROVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $733,193
- **Award type:** 5
- **Project period:** 2022-08-19 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873307

## Citation

> US National Institutes of Health, RePORTER application 10873307, Molecular Antecedents of Miscarriage (5R01HD105358-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873307. Licensed CC0.

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