Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome 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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► Demonstrates ability of vinclozolin to induce epigenetic transgenerational inheritance of reproductive disease in the outbred mouse model, but not inbred mouse model.
► Demonstrates epigenetic transgenerational inheritance of modifications in the mouse sperm epigenome.
► Demonstrates inbreeding depression of environmental induced epigenetic transgenerational inheritance.
► Demonstrates epigenetic transgenerational inheritance of a high incidence of male and female adult onset disease.