Abstract
Exposure to vinclozolin has been shown to induce the epigenetic transgenerational inheritance of increased susceptibility to disease, and to induce transgenerational changes to the epigenome. In the current study, gestating F0 generation rats were exposed to vinclozolin, and the subsequent F1, F2 and transgenerational F3 generations were evaluated for diseases and pathologies. F1 and F2 generation rats exhibited few abnormalities. However, F3 generation rats showed transgenerational increases in testis, prostate, and kidney disease, changes in the age of puberty onset in males, and an increased obesity rate in females. Overall there was an increase in the rate of animals with disease, and in the incidence of animals with multiple diseases. The objective of the current study was to analyze the sperm epigenome of F3 generation rats with specific abnormalities and compare them to rats without those abnormalities, in an effort to find epigenetic biomarkers of transgenerational disease. Unique signatures of differential DNA methylation regions (DMRs) in sperm were found that associated with testis disease, prostate disease and kidney disease. Confounding factors identified were the presence of multiple diseases in the analysis and the limited number of animals without disease. These results further our understanding of the mechanisms governing epigenetic transgenerational inheritance, and may lead in the future to the use of epigenetic biomarkers that will help predict an individual’s susceptibility for specific diseases.
Highlights
Epigenetic transgenerational inheritance involves the germline transmission of epigenetic information and phenotypic change across generations in the absence of any continued direct environmental exposure or genetic manipulation [1, 2]
The pathologies for each tissue were analyzed according to specific parameters and the rate of disease was determined for each tissue type and generation as described in the Methods [29]
The objectives of the current study were to investigate the epigenetic transgenerational inheritance of disease and abnormalities after ancestral exposure of gestating rats to vinclozolin, and to characterize the associated molecular epigenetic changes that were found in F3 generation sperm associated with specific diseases
Summary
Epigenetic transgenerational inheritance involves the germline transmission of epigenetic information and phenotypic change across generations in the absence of any continued direct environmental exposure or genetic manipulation [1, 2]. Transgenerational sperm epimutation biomarkers for specific disease analysis, decision to publish, or preparation of the manuscript
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