# Project-003

> **NIH NIH P20** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $268,835

## Abstract

Polycystic ovarian syndrome (PCOS) is a condition that affects 7-10% of women in their reproductive years, 
accounting for roughly 5 million women in the United States. Approximately, 80% of PCOS women suffer from 
hyperandrogenemia increasing the risk for developing comorbidities, such as obesity, chronic inflammation, 
increased blood pressure, type II diabetes, insulin resistance, dyslipidemias, and hyperleptinemia. In addition, 
approximately 42% of PCOS women suffer from gastrointestinal (GI) symptoms, such as abdominal pain, 
constipation, diarrhea, and/or bloating. Many of these symptoms are associated with sub-acute GI inflammation. 
Metformin, a common treatment for metabolic dysfunction in PCOS women, causes GI side effects, often 
resulting in patient non-compliance with treatment. However, the mechanisms that contribute to these GI 
symptoms are unknown. My exciting preliminary data in the hyperandrogenemic female (HAF) rat model of 
PCOS show mitochondrial dysfunction, increased mitochondrial reactive oxygen species (mtROS), and 
inflammation in the colon. Furthermore, my preliminary data show that colonic mtROS and inflammation are 
further increased in HAF rats given metformin. We hypothesize then: 1) the development of sub-acute GI 
inflammation in PCOS women is due to androgen- and AR-mediated impairment of colonic mitochondrial 
oxidative phosphorylation, leading to increased mtROS, gut dysbiosis, and inflammation that is further 
exacerbated by metformin; 2) the use of a mitochondrial targeted antioxidant therapy, such as MitoTEMPO, will 
improve mitochondrial function, decrease mtROS and inflammation, thus preventing development of sub-acute 
GI inflammation in PCOS women. These hypotheses will be tested our well characterized and clinically relevant 
model of PCOS, the HAF rat, in the following specific aims: Aim 1: To test the hypothesis that colon mitochondrial 
dysfunction and increased mtROS in HAF rats is linked to increased gut dysbiosis and sub-acute GI 
inflammation, and that mitochondrial-targeted antioxidant therapies, such as MitoTEMPO, will attenuate these 
changes; Aim 2: To test the hypothesis that metformin in the HAF rat exacerbates colonic mitochondrial 
dysfunction increasing gut dysbiosis and inflammation, and that addition of an antioxidant, such as MitoTEMPO, 
will improve the mitochondrial function with metformin.

## Key facts

- **NIH application ID:** 10657011
- **Project number:** 2P20GM121334-06
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Kristin Shirey Edwards
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $268,835
- **Award type:** 2
- **Project period:** 2017-06-08 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657011

## Citation

> US National Institutes of Health, RePORTER application 10657011, Project-003 (2P20GM121334-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10657011. Licensed CC0.

---

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