Abstract
BackgroundEnvironmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm.MethodsGestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated.ResultsDNA methylation and ncRNA were altered in each generation sperm with the direct exposure F1 and F2 generations being predominantly distinct from the F3 generation epimutations. The piRNA and small tRNA were the most predominant classes of ncRNA altered. A highly conserved set of histone retention sites were found in the control lineage generations which was not significantly altered between generations, but a large number of new histone retention sites were found only in the transgenerational generation DDT lineage sperm.ConclusionsTherefore, all three different epigenetic processes were concurrently altered as DDT induced the epigenetic transgenerational inheritance of sperm epimutations. The direct exposure generations sperm epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene associations with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Observations demonstrate all three epigenetic processes are involved in transgenerational inheritance. The different epigenetic processes appear to be integrated in mediating the epigenetic transgenerational inheritance phenomenon.
Highlights
Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease through the germline
A control generation lineage involved the exposure during day 8–14 of gestation to vehicle dimethyl sulfoxide (DMSO) alone
The sperm samples were collected from the cauda epididymis and sonication used to destroy any contaminating somatic cells and partially remove the tails from the sonication-resistant heads of the sperm as described in “Methods”
Summary
Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. A variety of environmental factors have been shown to promote the germline-mediated epigenetic transgenerational inheritance of disease and phenotypic variation [1, 2]. This includes abnormal nutrition (caloric restriction or high-fat diets), stress [3,4,5] and toxicants [1, 6]. Environmental impacts on the epigenetic transgenerational inheritance of phenotypic variation for subsequent generations appear to have an important role in evolutionary biology [23]. Elucidation of the molecular mechanisms involved in environmentally induced epigenetic transgenerational inheritance is important to fully understand disease etiology and evolution
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