# Sterile Inflammation at the Maternal-Fetal Interface and Fetal Immune Programming in a Non-Human Primate Model

> **NIH NIH K01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $219,456

## Abstract

Although it is recognized that systemic maternal immune responses influence the fetus, how local decidual and
placental inflammation, in the absence of an infectious agent, impacts the developing fetal immune system is
not understood. Developing a deeper understanding of decidual/placental inflammation will provide opportunities
for the development of targeted therapeutics either in utero or once offspring are born. Thus, the long-term goals
of this project are to understand how the in utero environment impacts the developing fetal immune system, and
to assess the long-term immunological consequences. The central hypothesis is that sterile inflammation at
the maternal-fetal interface (MFI) leads to skewing of the fetal immune system towards a pro-
inflammatory phenotype. To understand how sterile inflammation affects the fetal immune system, Tisseel, a
binary product where fibrinogen and thrombin are co-delivered to create rapid clotting, will be injected to the MFI
of pregnant rhesus macaques (Macaca mulatta), resulting in clotting and placental infarct development, leading
to necrosis and inflammation.
Specific Aim 1: To test the hypothesis that Tisseel injection into the MFI leads to sterile inflammation of
the decidua and placenta. Tisseel or sterile saline will be injected into the MFI in the late second trimester/early
third trimester (~GD90) of pregnant rhesus macaques. At ~GD155, the placenta and fetus will be obtained and
weighed, and the fetus will be euthanized. MFI tissues will be processed for histopathology, molecular and
immunological analyses, including spectral flow cytometry, scRNA-seq and Spatial Transcriptomics.
Specific Aim 2: To test the hypothesis that Tisseel injection into the MFI leads to fetal immune system
programming towards a proinflammatory phenotype. At experimental delivery, the fetus will be euthanized,
fetal tissues will be collected and mononuclear cell (MC) suspensions prepared. MCs will be analyzed for gene
expression (scRNA-seq) and chromatin accessibility (scATAC-seq).
Overall, the proposed project will address how sterile inflammation at the MFI impacts the developing immune
system. Because the fetal immune system is pliable, it makes this developmental stage an attractive opportunity
for targeted therapeutics that could prevent long-term health consequences. Completion of this K01 proposal
will also allow me to gain training in the development and use of experimental NHP models of pregnancy
complications, skills in advanced data analysis, and understanding of the fetal immune system. This will facilitate
my transition into an independent investigator in maternal-fetal health.

## Key facts

- **NIH application ID:** 10864406
- **Project number:** 1K01AI182448-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jessica Vazquez
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $219,456
- **Award type:** 1
- **Project period:** 2024-08-21 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864406

## Citation

> US National Institutes of Health, RePORTER application 10864406, Sterile Inflammation at the Maternal-Fetal Interface and Fetal Immune Programming in a Non-Human Primate Model (1K01AI182448-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10864406. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*