# Uterine infection and infertility: how microbial infection of the reproductive tract causes ovarian dysfunction.

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $316,909

## Abstract

Project summary
Bacterial infections of the female reproductive tract are common in both women and dairy cows. These uterine
infections cause infertility in both species, but the specific mechanisms resulting in a failure to conceive remains
unclear. Emerging evidence suggest that the infection impacts ovarian health, and that ovarian problems are
important causes of the infertility associated with uterine infection. Pathogen-associated molecules which initiate
inflammation are concentrated in the follicular fluid of dairy cows with uterine infection and ovarian function is
disrupted resulting in extended luteal phases, less sex hormone production, localized inflammatory responses
and reduced oocyte quality. Furthermore, exposure of bovine ovarian explants or mice to pathogen-associated
molecules accelerates activation of the primordial follicle reserve, suggesting that infection may deplete the total
number of follicles available in the ovary and reduce overall long-term fertility. In women, pelvic inflammatory
disease results from bacterial infection of the reproductive tract with common sexually transmitted pathogens.
Infertility affects 10% of PID patients, and ovarian pathology is a component of this disease, including depletion
of the follicle reserve. In addition, a higher proportion of IVF patients have suffered uterine infection, while
patients with elevated Chlamydia antibody titers or pathogen-associated molecules in the reproductive tract have
poor ovarian response and lower pregnancy rates.
We hypothesize that pathogen-associated molecules, and ovarian follicle inflammatory responses to
these molecules, compromises oocyte health and depletes the ovarian follicle reserve. This project will
utilize an animal model of uterine infection to study the mechanisms of ovarian dysfunction in dairy cows. Aim 1
will focus on the impact of infection on the oocyte itself, while Aim 2 will focus on effects of uterine infection on
ovarian follicle dynamics. These studies will allow us to determine the impact of infection on the oocyte and
ovarian follicle in an appropriate in vivo system. In parallel we will utilize in vitro cellular and molecular techniques
to determine the mechanisms by which infection results in ovarian dysfunction. Taken together we anticipate
finding common mechanisms that link pathogen-associated molecules and inflammation with the dysfunction of
oocytes and ovarian follicles.
These discoveries will provide target mechanisms of action for using therapeutics to limit the impact of uterine
disease on ovarian health. By understanding these mechanisms of ovarian dysfunction we can help protect
fertility, or minimize the impact of infection on the ovary, by using pharmacological manipulations of the immune
system and signaling pathways involved in infection-mediated infertility. The benefit of these studies to the NIH
and USDA will be to increase the health and fecundity of women and dairy cows, resulting in more positive
pregnancy...

## Key facts

- **NIH application ID:** 9947958
- **Project number:** 5R01HD084316-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** John J Bromfield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $316,909
- **Award type:** 5
- **Project period:** 2016-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947958

## Citation

> US National Institutes of Health, RePORTER application 9947958, Uterine infection and infertility: how microbial infection of the reproductive tract causes ovarian dysfunction. (5R01HD084316-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9947958. Licensed CC0.

---

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