Environmentally induced epigenetic transgenerational inheritance of disease susceptibility

Abstract

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology.

Figure 1

Schematic of environmentally induced epigenetic transgenerational inheritance in F3 generation. Direct exposure is shown in the F0, F1, and F2 generations.

Figure 2

Venn diagram of transgenerational sperm epimutations associated with different exposure groups showing a number of common epimutations in the F3 generation of rats due to ancestral exposure of F0 generation gestating females to vinclozolin, dioxin, pesticide, plastics or hydrocarbons. Modified from [40].