Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease

Matthew D Anway; Michael K Skinner

doi:10.1002/pros.20724

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Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease

Accepted manuscript

Open access

Peer reviewed

Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease

Matthew D Anway and Michael K Skinner

The Prostate, Vol.68(5), pp.517-529

04/01/2008

DOI: https://doi.org/10.1002/pros.20724

Handle:

https://hdl.handle.net/2376/103236

PMCID: PMC5940006

PMID: 18220299

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Abstract

Receptors, Tumor Necrosis Factor - metabolism

Prostatic Diseases - metabolism

Calcium - metabolism

Gene Expression Regulation, Developmental - drug effects

Androgen Antagonists - pharmacology

Gene Expression Profiling

Wnt Proteins - metabolism

Rats, Sprague-Dawley

Prenatal Exposure Delayed Effects - metabolism

Prostate - metabolism

Prenatal Exposure Delayed Effects - genetics

Prostate - pathology

Sex Determination Processes

Epigenesis, Genetic - genetics

Prostate - drug effects

Female

Oxazoles - pharmacology

Prostatic Diseases - genetics

Prostatic Secretory Proteins - metabolism

Endocrinology

Pregnancy

Phenotype

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.

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Title: Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease
Creators: Matthew D Anway - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA
Michael K Skinner
Publication Details: The Prostate, Vol.68(5), pp.517-529
Academic Unit: Biological Sciences, School of
Publisher: United States
Grant note: R01 ES012974 / NIEHS NIH HHS
Identifiers: 99900546701701842
Language: English
Resource Type: Accepted manuscript