# PFAS increases susceptibility to infection-mediated PTB

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2024 · $533,723

## Abstract

PROJECT SUMMARY
Preterm birth (PTB) and related intrauterine growth retardation (IUGR) affects 15 million babies a year globally
(~11% of births) and is linked to chronic diseases in adulthood. Infection-mediated PTB is associated with ~40%
of all PTBs, but not all maternal infections elicit PTB. The placenta is a primary mediator of this protection and
expresses protective Interferons (e.g., IFNb) which play a critical role in placental immune regulation. Co-I Gil
Mor has shown that downregulation of protective IFNb at the site of the placenta allows for a secondary bacteria
insult to elicit an uncontrolled inflammatory reaction that would otherwise have been benign. Recent
epidemiological and preclinical work shows that certain classes of environmental pollutants are
immunosuppressive and can inhibit IFN signaling. Per-and poly fluoroalkyl substances (PFAS) are a class of
ubiquitous man-made chemicals utilized for their surfactant properties in cookware, clothing, and carpets as well
as in foams used by firefighters and are found in the environment as mixtures. A handful of model PFAS have
been associated with preterm birth and decreased fetal growth. PFAS are established immunosuppressants
have reproducibly been shown to be associated with decreased IFN signaling in mice or humans and have been
linked to increased severity or incidence of infections. PFAS target the placenta and can decrease IFN signaling
in trophoblasts, but mechanistic studies investigating the role of decreased IFN as it relates to increased
susceptibility to a second hit during pregnancy are lacking. Thus, we hypothesize that PFAS exposure leads to
dysregulation of type 1 (i.e., IFNb) and/or type 2 (IFNg) responses in the placenta and is responsible for a
dysregulated inflammatory response to a secondary bacterial infection resulting in IUGR and PTB.
IFN signaling can be regulated by modulating IFN levels at the site of infection, or through regulation of IFN
receptors by post-translational modifications (PTMs), primarily by glycosylation. Biochemical labeling tools now
exist that allow for spatial analysis of glycosylated proteins at the resolution of single cells. No group has used
sugar labeling to track effects of PFAS on placental inflammation, especially as it relates to IFNs.
This Katz award will allow Dr. Petriello, a toxicologist and early-stage investigator to transition to study
inflammation within critical windows of susceptibility (pregnancy) and impacts on placental health and birth
outcomes. For this Katz award we will expose pregnant mice to concentrations of PFAS previously shown to
decrease IFN signaling as well as lead to IUGR, and then expose to a bacterial stressor which we predict will
elicit preterm delivery. Our aims are: 1. To test the hypothesis that maternal exposures to PFAS lead to
decreased IFN signaling and induce placental toxicity. 2. To test the hypothesis that N- and O-glycoprotein
distribution is altered specifically in spongiotrophoblas...

## Key facts

- **NIH application ID:** 10768105
- **Project number:** 1R01ES035692-01A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Michael Curtis Petriello
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $533,723
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768105

## Citation

> US National Institutes of Health, RePORTER application 10768105, PFAS increases susceptibility to infection-mediated PTB (1R01ES035692-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10768105. Licensed CC0.

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