# Maternal Nanomaterial Exposures: Fetal Microvascular Endpoints and Programming

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2020 · $337,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Despite the ubiquitous inclusion of engineered nanomaterials (ENM) in widespread applications, and their
projected proliferation in human endeavors; the consequences of maternal ENM inhalation on the developing
fetus and their impacts on future health are at best, vague. The advancement of nanotechnology, and “nano-
enabled” devices holds tremendous potential to advance human health exponentially, yet their unknown
health effects remain the critical rate limiting step. To date, studies focus on the fetal consequences of
artificially injected ENM or the ability of co-incubated ENM to cross the placenta. These fail to address the most
relevant health risks: 1) how do inhaled ENM impair the development of a healthy uterine vasculature, and
2) how do inhaled ENM impair placental development, or compromise its function? We will define the fetal
consequences of maternal ENM exposure in terms of altered mechanisms of uterine and placental vascular
health. ENM aerosol generation and rodent exposures will be performed in state-of-the-art inhalation exposure
facilities that have recently undergone significant expansion to directly meet the unique demands of this project.
AIM 1: Determine the impact of maternal ENM inhalation on uterine microvascular health during
gestation, and characterize the underlying mechanisms of dysfunction. We have defined the impact of
ENM inhalation on microvascular health, in the virgin uterus, with novel intravital microscopy studies. We now
expand this investigation to discrete stages of pregnancy. We hypothesize that the vasculogenic and angiogenic
mechanisms initiated by pregnancy and stimulate rapid microvascular network growth are susceptible targets of
the extrapulmonary mediators activated by ENM inhalation. AIM 2: Identify the impact of maternal ENM
inhalation on placental health during gestation and characterize the underlying mechanisms of
dysfunction. The placenta is a highly vascularized organ critical to fetal health/development, and is a systemic
target of extrapulmonary mediators. A second novel technique, the ex vivo perfused placenta will be used to test
our working hypothesis – maternal ENM inhalation disrupts placental vascular integrity via prostanoid and nitric
oxide mediated mechanisms. AIM 3: Define the cardiovascular health consequences that persist into
adulthood that stem from fetal epigenetic alterations that occur during maternal ENM inhalation during
gestation. We hypothesize that the hostile gestational environment created by maternal ENM inhalation
produces a genotype that not only displays impaired cardiovascular function, but also elevated sensitivity to
xenobiotic exposures in adulthood. Project outcomes: the fundamental relationships between uterine,
placental, and fetal microvascular health after maternal ENM exposure will be identified. We also expect to have
clarified many of the major mechanisms mediating these outcomes. Identifying these relationships will assist...

## Key facts

- **NIH application ID:** 9993525
- **Project number:** 5R01ES015022-13
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Timothy R Nurkiewicz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,500
- **Award type:** 5
- **Project period:** 2007-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993525

## Citation

> US National Institutes of Health, RePORTER application 9993525, Maternal Nanomaterial Exposures: Fetal Microvascular Endpoints and Programming (5R01ES015022-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993525. Licensed CC0.

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