Observations demonstrate a distinction between the direct exposure versus transgenerational epigenetic programming induced by environmental exposures and provide insights into the molecular mechanisms involved in the epigenetic transgenerational inheritance phenomenon.Īlterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease.īen Maamar, Millissia Sadler-Riggleman, Ingrid Beck, Daniel McBirney, Margaux Nilsson, Eric Klukovich, Rachel Xie, Yeming Tang, Chong Yan, Wei Skinner, Michael KĮpigenetic transgenerational inheritance of disease and phenotypic variation can be induced by several toxicants, such as vinclozolin. This may help explain the differences in disease and phenotypes between the direct exposure F1 generation and transgenerational F 3 generation. Observations suggest the direct exposure induced F1 generation sperm DMRs appear to promote in subsequent generations alterations in the germ cell developmental programming that leads to the distinct epimutations in the F 3 generation. Interestingly, the F1 generation DMRs were found to be fewer in number and for the most part distinct from the F 3 generation epimutations. Observations indicate needs to be considered. Bioinformatics analysis of the MeDIP-Seq data was developed and several different variations in the bioinformatic analysis were evaluated.
A protocol involving methylated DNA immunoprecipitation (MeDIP) followed by next- generation sequencing (Seq) was used in the current study. The current study was designed to investigate the actions of direct fetal exposure on the F1 generation rat sperm DMRs compared to the F 3 transgenerational sperm DMRs. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F 3 generation (great-grand-offspring) animals.
These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. Generational comparisons ( F1 versus F 3) of vinclozolin induced epigenetic transgenerational inheritance of sperm differential DNA methylation regions (epimutations) using MeDIP-Seq.īeck, Daniel Sadler-Riggleman, Ingrid Skinner, Michael KĮnvironmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g.
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