Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers

Carlos Guerrero-Bosagna; Trevor R Covert; Md M Haque; Matthew Settles; Eric E Nilsson; Matthew D Anway; Michael K Skinner

doi:10.1016/j.reprotox.2012.09.005

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Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers

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Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers

Carlos Guerrero-Bosagna, Trevor R Covert, Md M Haque, Matthew Settles, Eric E Nilsson, Matthew D Anway and Michael K Skinner

Reproductive toxicology (Elmsford, N.Y.), Vol.34(4), pp.694-707

12/2012

DOI: https://doi.org/10.1016/j.reprotox.2012.09.005

Handle:

https://hdl.handle.net/2376/106943

PMCID: PMC3513496

PMID: 23041264

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Abstract

Kidney - pathology

Apoptosis - drug effects

Flutamide - toxicity

Testis - drug effects

Ovarian Cysts - chemically induced

Prostate - pathology

DNA Methylation

Prostate - drug effects

Animals, Outbred Strains

Androgen Antagonists - toxicity

Epigenomics

Kidney - drug effects

Mice, Inbred Strains

Endocrine Disruptors - administration & dosage

Endocrine Disruptors - toxicity

Sperm Motility - drug effects

Oxazoles - toxicity

Testis - pathology

Oxazoles - administration & dosage

Androgen Antagonists - administration & dosage

Epigenetics

Pregnancy

Biomarkers

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

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Title: Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers
Creators: Carlos Guerrero-Bosagna - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, United States
Trevor R Covert
Md M Haque
Matthew Settles
Eric E Nilsson
Matthew D Anway
Michael K Skinner
Publication Details: Reproductive toxicology (Elmsford, N.Y.), Vol.34(4), pp.694-707
Academic Unit: Biological Sciences, School of
Publisher: United States
Grant note: R01 ES012974 / NIEHS NIH HHS
Identifiers: 99900546856501842
Language: English
Resource Type: Accepted manuscript