GSE113785
Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases
F0 generation rats were exposed to vinclozolin, and the subsequent F1, F2 and transgenerational F3 generations are evaluated for diseases and pathologies. 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 disease. The methylation of the F3 vinclozolin lineage rat samples was determined using MeDIP-seq. Unique signatures of differential DNA methylation regions (DMRs) in sperm were found that associated with testis disease, prostate disease and kidney disease, however, these signatures were not statistically significant. Overall design: Outbred gestating female rats were transiently exposed to a vehicle control or vinclozolin. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the vinclozolin lineage sperm from samples with different disease outcomes. MeDIP-seq was used to measure methylation in each sample.