# Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs

> **NIH NIH R00** · DARTMOUTH COLLEGE · 2022 · $235,143

## Abstract

PROJECT SUMMARY/ABSTRACT
Reduced fetal growth has been implicated in a broad range of adverse health outcomes. Growing evidence
suggests that toxic metal exposures adversely affect fetal growth, indicated by reduced fetal ultrasound
measurements and lower birth weight. Although most individuals are exposed simultaneously to multiple
metals, which may act additively or synergistically to reduce fetal growth, the majority of studies have focused
on the toxicity of individual metals. While the mechanisms underlying metal-induced reductions in fetal growth
are incompletely understood, there is evidence that epigenetic dysregulation, including altered microRNA
(miRNA) expression, contributes to these effects. In addition to epigenetically regulating gene expression,
maternal circulating miRNAs play important roles in maternal-placental-fetal crosstalk. However, the potential
role of maternal circulating miRNAs in mediating metal mixture effects on fetal growth is unknown. The goal of
the proposed project is to examine the impact of prenatal metal mixture exposures on fetal growth and to
determine whether altered maternal circulating miRNAs mediate these relationships. During the mentored K99
phase of this award, Dr. Howe will leverage existing data and biospecimens from 500 mother-newborn pairs in
the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, a low-
income predominately Hispanic pregnancy cohort based in Los Angeles, to investigate potential additive and
synergistic relationships between prenatal exposure to 15 metals and in utero growth and birth weight. To
accomplish this, she will expand metals exposure assessment in the MADRES pregnancy cohort and train in
methods for analyzing complex environmental mixtures, including weighted quantile sum regression and
Bayesian kernel machine regression. During the R00 phase, Dr. Howe will determine whether maternal
circulating miRNAs mediate metal mixture-fetal growth relationships, using structural equation models, and will
examine potential downstream effects by profiling mRNA expression levels within the maternal-placental-fetal
axis, using RNA-Seq, in a subset (N = 50) of mother-newborn pairs. Results from the proposed studies may be
used to improve the efficacy of public health interventions aimed at preventing metal-induced reductions in
fetal growth. Furthermore, they will increase knowledge of a potential underlying mechanism (altered maternal
circulating miRNAs) and may lead to the identification of early and relatively non-invasive biomarkers of metal
mixture exposures and reduced fetal growth. Dr. Howe has assembled a mentoring team, spanning the
University of Southern California, Boston University, and Emory University, with expertise in metals toxicity,
environmental mixtures modeling, epigenetic epidemiology, and perinatology. This team will provide ongoing
feedback and on-site training opportunities to complement coursework, workshops, and seminars,...

## Key facts

- **NIH application ID:** 10452576
- **Project number:** 5R00ES030400-05
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Caitlin Grace Howe
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,143
- **Award type:** 5
- **Project period:** 2020-07-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452576

## Citation

> US National Institutes of Health, RePORTER application 10452576, Prenatal Metal Mixtures, Fetal Growth, and the Role of MicroRNAs (5R00ES030400-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10452576. Licensed CC0.

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