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

Award Number: F31ES030968
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/21/2020
PERIOD OF PERFORMANCE END DATE: 06/06/2021

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$2,914 )
2023	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Environmental Health	000	2	11/23/2022	NON-COMPETING CONTINUATION	-$2,914
														Subtotal = -$2,914

Issue Date FY: 2021 ( Subtotal = $8,858 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Environmental Health	000	2	4/16/2021	NON-COMPETING CONTINUATION	$33,421
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Environmental Health	001	2	6/4/2021	NON-COMPETING CONTINUATION	-$24,563
														Subtotal = $8,858

Issue Date FY: 2020 ( Subtotal = $32,697 )
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Environmental Health	001	1	4/21/2020	NEW	$0
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Environmental Health	000	1	4/21/2020	NEW	$32,697
														Subtotal = $32,697

Grand Total All Awards = $38,641

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

Award Number: F31ES030968

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/21/2020

PERIOD OF PERFORMANCE END DATE: 06/06/2021

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