# The Role of Choriodecidual Infection in the Pathogenesis of Preterm Birth and Inflammatory Brain Injury

> **NIH NIH R00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $240,839

## Abstract

Summary
The objectives of this proposal are to assess the role of the early stages of ascending reproductive tract infection
(i.e. choriodecidual infection) in the initiation of maternal and fetal inflammatory responses that activate
mechanisms of inflammation and injury in the fetal brain. The central hypothesis is that maternal-fetal
inflammatory responses following choriodecidual infection with U. parvum initiate early processes of
preterm labor, prior to microbial invasion of the amniotic cavity, leading to the appearance of “sterile”
fetal inflammation and brain injury. The experimental paradigm [utilizes a chronically catheterized pregnant
rhesus monkey model of choriodecidual inoculation] with Ureaplasma parvum at 105dGA (term~168 days). We
predict this novel approach will mimic the natural course of ascending intra-uterine Ureaplasma infection during
human pregnancy, providing a model of infection-driven fetal inflammation, without direct microbial exposure of
the fetus. This will allow us to assess the [initiation of fetal inflammatory responses.] Preliminary data of co-
localization of hyaluronic acid with microgliosis suggests a novel mechanism by which perinatal inflammatory
brain injury is mediated. [Aspects of the preterm labor syndrome will be assessed to determine how
inflammatory mediators that lead to cervical ripening fetal membrane weakening and uterine contractility
may also affect the developing brain.] Histological assessments will determine the extent of deciduitis,
chorioamnionitis, and membrane structure and integrity. [Abdominal ultrasound and Bishop score will be
employed to determine cervical shortening and dilation, respectively.] Continuous physiological monitoring of
uterine pressure and serial sampling of amniotic fluid and maternal blood will occur via indwelling catheters
implanted at surgery. Pro-inflammatory mediator expression (cytokines, prostaglandins, MMPs) will be measured
in these samples, as well as in cord blood, fetal CSF and fetal brain and lung tissue. At delivery, fetal brains will
be examined for gross pathological changes and histologic evidence of inflammation and injury. Specific markers
for oligodendrocyte maturation and microglial activation will be identified and correlated to MRI findings and
location of hyaluronic acid accumulation. Hyaluronic acid receptor and metabolite expression will also be
determined by immunohistochemistry. Major strengths of the proposal lie in the unique non-human primate
model of Ureaplasma choriodecidual infection based on preliminary data. This application and the associated
career development plan will provide a foundation for the Candidate’s continued independent research in the
fields of perinatal and reproductive biology. [Formal tuition in biostatistics, research design, lab
management/leadership coupled with specific training in neuroscience techniques, non-human primate
research skills and membership of the Brain & Behavioral Development research group p...

## Key facts

- **NIH application ID:** 10247825
- **Project number:** 5R00HD090229-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Meredith Anne Kelleher
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $240,839
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247825

## Citation

> US National Institutes of Health, RePORTER application 10247825, The Role of Choriodecidual Infection in the Pathogenesis of Preterm Birth and Inflammatory Brain Injury (5R00HD090229-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247825. Licensed CC0.

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