# Microvascular mechanisms of growth restriction after environmental toxicant exposure

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $45,342

## Abstract

PARENT GRANT ABSTRACT
The uterine circulation and placenta are specifically designed to regulate the flow of blood and transport of
essential nutrients to the fetus. Disruption of maternal hemodynamic regulation during pregnancy can adversely
impact fetal health, resulting in miscarriage and intrauterine growth restriction (IUGR). Current treatment options
for IUGR patients are extremely limited, focusing primarily on early delivery; thus, putting the mother and child
at risk for complications associated with preterm birth. Epidemiological studies indicate that pregnant women
exposed to fine particulate matter (PM) have a heightened risk of fetal loss and development of IUGR. We have
reproduced this phenomenon in laboratory rodent models, wherein animals exposed to nanosized titanium
dioxide (nano-TiO2) aerosols develop IUGR and suffer a greater number of `miscarriages' (fetal reabsorptions).
We have demonstrated that acute and chronic exposures significantly impair uterine vascular endothelium
dependent dilation, severely limiting maternal-to-fetal blood flow and impacting fetal growth. Unfortunately,
current research strategies have yet to elucidate the vascular mechanisms associated with the development of
IUGR after maternal particulate exposure. Based on previous findings, we hypothesize that maternal inhalation
of nano-TiO2 aerosols during pregnancy promotes the development of IUGR by disrupting endothelium-
dependent signaling cascades, resulting in a net reduction in uterine vasodilation and blood flow. We
further postulate that IUGR will be mitigated by improved vascular signaling and function after nutritional
supplementation with folic acid. Using novel approaches and methodologies, these studies will: (1) evaluate
uterine nitric oxide-driven vasodilation, (2) determine whether alterations in arachidonic acid metabolism impair
uterine vascular reactivity and impact placental perfusion, and (3) assess the therapeutic benefit of dietary folic
acid supplementation to improve utero-placental blood flow and attenuate the development of IUGR after
maternal exposure to nano-TiO2 aerosols. These studies are conceptually innovative as we will utilize our unique
resources to identify mechanistic targets within the utero-placental microcirculation and test directed nutritional
interventions for IUGR. This work is technically innovative as we will use novel methodologies developed for the
evaluation of environmental toxicity in maternal-fetal medicine. Overall, the successful completion of these
studies will: (1) create the conceptual framework to identify environmental exposure as a risk factor for the
development of IUGR; (2) reveal new mechanistic insight into the vascular pathogenesis resulting from
nanomaterial exposure; (3) provide a molecular basis to identify how nanomaterial exposure manifests as
vascular disruptions; and (4) identify mechanistic targets for therapeutic strategies to ameliorate microvascular
dysfunction and improve utero-...

## Key facts

- **NIH application ID:** 10359947
- **Project number:** 3R01ES031285-01A1S1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Phoebe Stapleton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $45,342
- **Award type:** 3
- **Project period:** 2021-06-04 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359947

## Citation

> US National Institutes of Health, RePORTER application 10359947, Microvascular mechanisms of growth restriction after environmental toxicant exposure (3R01ES031285-01A1S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10359947. Licensed CC0.

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