# Uterine microbiome: Functional significance in establishing the uterine program postpartum

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $315,192

## Abstract

PROJECT SUMMARY
Approximately one-third of postpartum cows develop uterine disease (metritis) within one week after calving
and 5% of all calvings result in death of the cow within 30 days due to metritis or other complications that
originate during calving. Postpartum uterine infection in women is less common, but approximately 10% of
pregnancy-related deaths in the United States are caused by puerperal genital tract infection. Cows with early
postpartum uterine disease will develop chronic inflammation of the uterus (endometritis or subclinical
endometritis; SCE). Chronic endometritis in women (pelvic inflammatory disease; PID) is similar to the bovine
disease and is caused by a variety of bacterial species. If left untreated, both SCE and PID cause infertility.
The inability to effectively treat uterine disease and restore fertility may be partially explained by a critical gap
in understanding of the uterine microbiome and its relationship to the disease status, uterine immune function,
inflammation, tissue regeneration, and long-term programming of uterine dysfunction. The goal of this
proposal is to understand the origins of uterine disease and the mechanisms through which uterine disease
programs subfertility and infertility. The studies begin with the virgin bovine uterus where the presence and
viability of the microbiome after first breeding will be determined (Aim 1; Study 1A & 1B). The microbiome of
first and second pregnancy will then be studied (Aim 1, Study 1C). Whether metritis during the early
postpartum period permanently damages the endometrium through structural and functional mechanisms and
whether systemic antibiotic treatment mitigates the effect is the subject of Aim 2. Finally, the embryotrophic
capacity of the diseased endometrium will be assessed (Aim 3). Collectively, the proposed investigations will
elucidate novel structural and functional mechanisms through which the microbiome programs fertility. The
research is innovative from both a conceptual and technical perspective. The uterine microbiome and its effect
on fertility is an exciting new area of research and conceptually innovative. The cow provides an innovative
model for uterine disease research due to the remarkable similarity between uterine disease states and
outcomes in cows and women. Whole genome metagenomic sequencing will be performed as this approach
will enable us to assess the entire microbiome. The transcriptome will be studied by using laser capture
microdissection (LCM) and RNA sequencing. Reduced representation bisulfite sequencing (RRBS) will be
used to identify patterns of DNA methylation associated with changes in the transcriptome. The proposed
studies will identify tissue-specific mechanisms through which the endometrium fails to establish a receptive
uterine environment and the cow fails to become pregnant. This fundamental knowledge is necessary to
develop innovative tools to diagnose, treat, and ameliorate the effects of uterine disease. I...

## Key facts

- **NIH application ID:** 10153837
- **Project number:** 5R01HD092254-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Matthew C Lucy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,192
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153837

## Citation

> US National Institutes of Health, RePORTER application 10153837, Uterine microbiome: Functional significance in establishing the uterine program postpartum (5R01HD092254-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10153837. Licensed CC0.

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