Phthalates are ubiquitous environmental pollutants found in plastic and PVC-containing devices. Human exposure to phthalates poses a serious risk to testicular function. Hallmarks of phthalate induced testicular injury include disruption of Sertoli-germ cell adhesion and FSH-stimulated cAMP accumulation by Sertoli cells. Although the mechanism of phthalate induced testicular injury is not known, these data suggest that both G protein-coupled receptor signaling and cell-cell adhesion are early targets of phthalate injury.Flamingo proteins contain extracellular cadherin cell-cell adhesion domains coupled to seven transmembrane helices, thus indicating their involvement in both cell-cell adhesion and G protein mediated signal transduction. Three Flamingo homologs are expressed in rat testis at the mRNA level, and their expression pattern is affected by phthalate exposure. The mRNA expression of Flamingo 1 and 2 decreased to 70% of control 3 hours post exposure and continued to decline at later time points. This grant proposal investigates the mechanism of phthalate induced testicular injury by examining this hypothesis: Phthalates induce phosphorylation, internalization and degradation of Flamingo 1 and 2 protein leading to Sertoli-germ cell detachment and germ cell apoptosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30ES011930-04
Application #
6929695
Study Section
Special Emphasis Panel (ZRG1-F10 (29))
Program Officer
Humble, Michael C
Project Start
2002-08-01
Project End
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$42,729
Indirect Cost
Name
Brown University
Department
Pathology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912