# Developmental origins of prostate-related urinary dysfunction in adult males: TCDD exposure increases prostatic noradrenergic innervation and smooth muscle contraction

> **NIH NIH F31** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $8,858

## Abstract

PROJECT ABSTRACT
Prostate-related urinary symptoms, including weak stream and increased frequency of urination especially at
night, affect most men of advancing age and command billions of dollars annually. Although benign prostatic
enlargement was originally thought to be the only risk factor, new evidence suggests additional mechanisms may
contribute. Exposure to the persistent environmental contaminant 2,3,7,8 tetrachlorobenzo-p-dioxin (TCDD),
during development (in utero) and via lactation, thickens prostatic smooth muscle in monkeys and mice and
exacerbates urinary dysfunction in a mouse model of benign prostatic hyperplasia. TCDD-mediated prostatic
smooth muscle thickening is likely important because smooth muscle dysfunction is proposed as a major
mechanism of prostate-mediated voiding dysfunction in men and is a key target for current therapeutics. The
proposed studies test the hypothesis that in utero and lactational TCDD exposure causes smooth muscle and
voiding dysfunction by a mechanism involving impaired prostatic neuroanatomical development. These studies
are innovative because they use a novel axon quantification method to evaluate the impact of TCDD on
noradrenergic axon density, deploy fluorescent encoded calcium sensors in prostate smooth muscle to quantify
the impact of TCDD on nerve-evoked smooth muscle contraction, and leverage contrast-enhanced ultrasound to
test whether TCDD impedes the passage of urine through the urethra. The proposed studies will develop the
candidate's career by building technical competency in toxicology, neuroscience, and physiology, assay design,
and collaborative science while also developing skills in business, leadership, and networking.

## Key facts

- **NIH application ID:** 10149161
- **Project number:** 5F31ES030968-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Anne Turco
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,858
- **Award type:** 5
- **Project period:** 2020-04-21 → 2021-06-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149161

## Citation

> US National Institutes of Health, RePORTER application 10149161, Developmental origins of prostate-related urinary dysfunction in adult males: TCDD exposure increases prostatic noradrenergic innervation and smooth muscle contraction (5F31ES030968-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10149161. Licensed CC0.

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