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| Status |
Public on Jun 20, 2008 |
| Title |
Transgenerational effects of the endocrine disruptor Vinclozolin on the prostate transcriptome and adult onset disease |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study.
METHODS: Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation.
RESULTS: Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd).
CONCLUSIONS: The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease.
Keywords: expression analysis, transgenerational changes due to Vinclozolin
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| Overall design |
RNA samples from ventral prostate or prostate epithelium from F3 generation control rats are compared to corresponding tissues from F3 generation Vinclozolin treated rats
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| Web link |
http://www.skinner.wsu.edu/
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| Contributor(s) |
Anway M, Skinner MK |
| Citation(s) |
18220299 |
| Submission date |
Jun 20, 2008 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Michael K Skinner |
| E-mail(s) |
skinner@mail.wsu.edu
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| Organization name |
WSU
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| Department |
SBS
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| Street address |
Abelson 507
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| City |
Pullman |
| State/province |
WA |
| ZIP/Postal code |
99163 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (8)
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| GSM299114 |
F3-Control Ventral Prostate, replica 1 |
| GSM299115 |
F3-Control Ventral Prostate, replica 2 |
| GSM299116 |
F3-Vinclozolin Ventral Prostate, replica 1 |
| GSM299117 |
F3-Vinclozolin Ventral Prostate, replica 2 |
| GSM299118 |
F3-Control Prostate Epithelium, replica 1 |
| GSM299119 |
F3-Control Prostate Epithelium, replica 2 |
| GSM299120 |
F3-Vinclozolin Prostate Epithelium, replica 1 |
| GSM299121 |
F3-Vinclozolin Prostate Epithelium, replica 2 |
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| Relations |
| BioProject |
PRJNA105633 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11842_RAW.tar |
16.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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