Sunday, August 3, 2025 8/3/2025

CELL INTERACTIONS IN MALE REPRODUCTIVE PHTHALATE INJURY

Award Number: R01ES011632
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/25/2002
PERIOD OF PERFORMANCE END DATE: 02/28/2006

Group Awards By:

View Award Description

CELL INTERACTIONS IN MALE REPRODUCTIVE PHTHALATE INJURY - DESCRIPTION (provided by applicant): Phthalates are ubiquitous environmental contaminants present in soft plastics and PVC-containing devices, resulting in significant human exposure through contamination of food and medical products. The recently completed study by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction noted there was "serious concern" that some human phthalate exposures are sufficiently high to adversely affect male reproductive function. Despite being the most studied testicular toxicant, the mechanism of phthalate-induced testicular injury is not known. Therefore, the long-term objective of this research is to determine the mechanism of phthalate-induced testicular injury in molecular detail. Hallmarks of phthalate testicular injury are an initial action on Sertoli cells, disruption of Sertoli cell FSH-induced cAMP generation, and the loss of Sertoli-germ cell adhesion. These historical data suggest that both signaling from G protein-coupled receptors and Sertoli-germ cell adhesion proteins are proximal targets of phthalate injury. Recently, putative Sertoli cell G protein-coupled receptors that are cell-cell adhesion proteins (flamingos) were discovered in testis, making such proteins attractive phthalate targets. The specific down-regulation of testicular flamingo mRNA during early stages of phthalate exposure confirmed that flamingo biology was compromised by phthalates. Because of these observations, this grant proposal investigates the mechanism of phthalate-induced testicular injury by examining the following working hypothesis: phthalates induce the phosphorylation, internalization and degradation of flamingo l and 2 protein leading to Sertoli-germ cell detachment and germ cell apoptosis. Three specific aims will test this hypothesis by 1) localizing flamingo 1 and 2 to specific testis cell types, 2) examining both qualitative and quantitative changes in flamingo proteins during phthalate exposure, and 3) determining if disruption of flamingo protein mimics the phenotype produced by phthalate injury.


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: 2005 ( Subtotal = $301,525 )
2005	2005	CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY	POST OFFICE BOX 12137	RESCH TRIANGLE PK	NC	27709		USA	Environmental Health	000	5	3/14/2005	NON-COMPETING CONTINUATION	$301,525
														Subtotal = $301,525

Issue Date FY: 2004 ( Subtotal = $301,525 )
2004	2004	CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY	POST OFFICE BOX 12137	RESCH TRIANGLE PK	NC	27709		USA	Environmental Health	000	4	2/6/2004	NON-COMPETING CONTINUATION	$301,525
														Subtotal = $301,525

Issue Date FY: 2003 ( Subtotal = $273,978 )
2003	2003	CHEMICAL INDUSTRY INSTITUTE OF TOXICOLOGY	POST OFFICE BOX 12137	RESCH TRIANGLE PK	NC	27709		USA	Environmental Health	000	3	9/8/2003	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$168,131
2003	2003	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Environmental Health	000	2		NON-COMPETING CONTINUATION	$105,847
														Subtotal = $273,978

Issue Date FY: 2002 ( Subtotal = $262,917 )
2002	2002	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Environmental Health	000	1	6/21/2002	NEW	$262,917
														Subtotal = $262,917

Grand Total All Awards = $1,139,945

Top

All Categories

About

Search

Reports

Data Submission

Award Information

CELL INTERACTIONS IN MALE REPRODUCTIVE PHTHALATE INJURY

Award Number: R01ES011632

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/25/2002

PERIOD OF PERFORMANCE END DATE: 02/28/2006

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer