# Toxicant Exposure Impacts Host-pathogen interactions within the Reproductive Tract

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Project Summary
Exposure to persistent environmental toxicants (such as dioxin) is a global problem, but disproportionately
affects Veterans who were exposed dioxin derived from burn pits or Agent Orange. Dioxin exposure has been
linked to diminished fertility and an increased risk of preterm birth in both males and females, even when the
exposure occurred in utero. Recent studies indicate that female Veterans have increased risk of preterm birth
associated with recent deployment, underscoring the need for better diagnostics and interventions to eliminate
the risk of preterm birth associated with the unique environmental stressors encountered by Veterans.
However, little is known about the underlying molecular factors that contribute to this risk. We hypothesize that
exposure to environmental toxicants leads to perturbations in the host immune system programme which lead
to increased susceptibility to inflammatory insults (such as infection) that can lead to preterm birth.
Streptococcus agalactiae or Group B Streptococcus (GBS) is a bacterium that can cause invasive reproductive
tract infections that lead to preterm birth. We have new and exciting data indicating females exposed to
toxicant have increased susceptibility to GBS infection leading to adverse pregnancy outcomes. We also have
strong data showing that toxicant exposure alters placental macrophage antimicrobial activity such as reactive
oxygen species production, and GBS survival within macrophages. We also have strong data which supports
that macrophages are critical mediators of immune homeostasis during pregnancy that also play a role in
invasive GBS infections. Placental macrophages elaborate extracellular traps in response to GBS infectious
insult and these traps are decorated with matrix metalloproteinases which are involved in the degradation of
cell-to-cell matrices in gestational tissues that are important for maintaining a stable pregnancy. This
translational research seeks to understand how toxicant exposure alters host susceptibility to preterm birth
(using invasive infection as a model) and contributes to disease progression by modulating the host immune
system. This knowledge may lead to new approaches for the prevention and treatment of reproductive tract
infections which often lead to preterm birth, neonatal sepsis, maternal bacteremia, and fetal demise as well as
ameliorate fertility issues associated with toxicant exposure.

## Key facts

- **NIH application ID:** 10125254
- **Project number:** 1I01BX005352-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jennifer A Gaddy
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125254

## Citation

> US National Institutes of Health, RePORTER application 10125254, Toxicant Exposure Impacts Host-pathogen interactions within the Reproductive Tract (1I01BX005352-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10125254. Licensed CC0.

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