In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs ventral prostate development in mice by inhibiting prostatic epithelial bud formation (budding) from the fetal urogenital sinus (UGS). While it is the epithelial component of the UGS that gives rise to prostatic buds, it is the surrounding UGS mesenchyme (UGM) that contains the androgen receptors (AR) that drive budding and the aryl hydrocarbon receptors (AhR) that mediate budding inhibition by TCDD. The proposed research will identify those genes in the UGM that are direct targets of the AR and the AhR through the use of chromatin immunoprecipitation (ChlP) assays, which identify gene promoters actively bound to transcription factors. This research will also identify genes whose expression is androgen- and TCDD-responsive through DNA microarray analysis of whole UGS gene expression. UGSs will be analyzed from wild-type and AR-deficient (Tfm) male C57BL/6J fetuses exposed in utero to vehicle or TCDD during day 15 to day 16 of gestation, the critical window for budding inhibition by TCDD. Little information is currently available regarding the mechanisms of TCDD-induced budding inhibition. This work will facilitate the identification of key signaling cascades involved in budding inhibition by identifying the earliest AhR-DNA binding events following exposure of the UGS to TCDD.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HD049323-01
Application #
6893535
Study Section
Special Emphasis Panel (ZRG1-IDM-L (29))
Program Officer
Rankin, Tracy L
Project Start
2005-02-01
Project End
2009-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$33,962
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Pharmacy
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Allgeier, Sarah H; Lin, Tien-Min; Moore, Robert W et al. (2010) Androgenic regulation of ventral epithelial bud number and pattern in mouse urogenital sinus. Dev Dyn 239:373-85
Vezina, Chad M; Hardin, Heather A; Moore, Robert W et al. (2010) 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits fibroblast growth factor 10-induced prostatic bud formation in mouse urogenital sinus. Toxicol Sci 113:198-206
Allgeier, Sarah Hicks; Vezina, Chad M; Lin, Tien-Min et al. (2009) Estrogen signaling is not required for prostatic bud patterning or for its disruption by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 239:80-6
Allgeier, Sarah Hicks; Lin, Tien-Min; Vezina, Chad M et al. (2008) WNT5A selectively inhibits mouse ventral prostate development. Dev Biol 324:10-7
Vezina, Chad M; Allgeier, Sarah Hicks; Moore, Robert W et al. (2008) Dioxin causes ventral prostate agenesis by disrupting dorsoventral patterning in developing mouse prostate. Toxicol Sci 106:488-96
Vezina, Chad M; Allgeier, Sarah H; Fritz, Wayne A et al. (2008) Retinoic acid induces prostatic bud formation. Dev Dyn 237:1321-33
Cook, Crist; Vezina, Chad M; Allgeier, Sarah H et al. (2007) Noggin is required for normal lobe patterning and ductal budding in the mouse prostate. Dev Biol 312:217-30