The authors declare that they have no competing financial interests.
Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease†
Article first published online: 25 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 68, Issue 5, pages 517–529, 1 April 2008
How to Cite
Anway, M. D. and Skinner, M. K. (2008), Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease. Prostate, 68: 517–529. doi: 10.1002/pros.20724
- Issue published online: 22 FEB 2008
- Article first published online: 25 JAN 2008
- Manuscript Accepted: 15 NOV 2007
- Manuscript Received: 17 JUL 2007
- National Institute of Environmental Health Sciences (NIEHS)
- ventral prostate;
- endocrine disruptor;
- prostate disease;
- embryonic exposure
The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study.
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.
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).
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. Prostate 68: 517–529, 2008. © 2008 Wiley-Liss, Inc.