# Contribution of obesity-environment interaction in bladder dysfunction

> **NIH NIH R03** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $77,750

## Abstract

Lower urinary tract symptoms (LUTS) such as urgency and frequent urination (overactive bladder)
impose a significant healthcare burden and reduce quality of life. Factors which contribute to onset
and severity of symptoms are not completely understood but are likely multifactorial, therefore we
propose to lead new efforts in understanding interactions which may contribute to LUTS. In other
organs, developmental exposures to environmental toxicants alone or in combination with a
second stressor can influence disease progression later in life. Obesity is also a risk factor for
many diseases including overactive bladder. Whether an obesity-environmental interaction
paradigm exists for LUTS is unknown but could be a new risk factor for urinary disease. Here we
propose to test the hypothesis that developmental exposure to polychlorinated biphenyls (PCBs)
exacerbates urinary dysfunction when mice are later challenged with a common second stressor,
diet induced obesity. Our preliminary data indicate that developmental exposure to environmental
toxicants, polychlorinated biphenyls (PCBs), in mice, leads to small, more frequent voids as young
adults. Other studies have shown that obesity is linked to bladder dysfunction, with high fat diets
linked to small more frequent voids in rodents. Preliminary data indicate that developmental
exposure to PCBs or a high fat diet alone increase F4/80+ macrophages in female bladder. Our
expected results are that combined exposure to PCBs and high fat diet together will exacerbate
increased voiding frequency. We also hypothesize that bladder inflammation, specifically
increased macrophages, are a convergent target for both hits thus expected results are that
combined exposure will lead to increased number of macrophages in bladder compared to either
hit alone. Whether macrophages are the major inflammatory mediator and whether elevated
macrophage numbers result from bladder resident macrophages or infiltrating monocytes which
differentiate into macrophages is unknown but of potential clinical relevance since therapeutic
approaches to block infiltrating monocytes could be employed. We will test our hypothesis in three
aims. The first testing whether developmental PCB exposure combined with a high fat diet in
adulthood increases voiding frequency and decreases voided urine volume in mice compared to
either stressor alone. The second testing whether developmental PCB exposure combined with
a high fat diet exacerbates bladder inflammation by increasing the abundance of infiltrating
monocytes which differentiate into macrophages. The third testing whether infiltrating monocytes
contribute to PCB or high fat diet induced voiding dysfunction.

## Key facts

- **NIH application ID:** 10450943
- **Project number:** 1R03ES033304-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Kimberly Preston Keil Stietz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,750
- **Award type:** 1
- **Project period:** 2022-03-17 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450943

## Citation

> US National Institutes of Health, RePORTER application 10450943, Contribution of obesity-environment interaction in bladder dysfunction (1R03ES033304-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10450943. Licensed CC0.

---

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