Role of epigenetic transgenerational inheritance in generational toxicology

Abstract

Many environmental toxicants have been shown to be associated with the transgenerational inheritance of increased disease susceptibility. This review describes the generational toxicity of some of these chemicals and their role in the induction of epigenetic transgenerational inheritance of disease. Epigenetic factors include DNA methylation, histone modifications, retention of histones in sperm, changes to chromatin structure, and expression of non-coding RNAs. For toxicant-induced epigenetic transgenerational inheritance to occur, exposure to a toxicant must result in epigenetic changes to germ cells (sperm or eggs) since it is the germ cells that carry molecular information to subsequent generations. In addition, the epigenetic changes induced in transgenerational generation animals must cause alterations in gene expression in these animals' somatic cells. In some cases of generational toxicology, negligible changes are seen in the directly exposed generations, but increased disease rates are seen in transgenerational descendants. Governmental policies regulating toxicant exposure should take generational effects into account. A new approach that takes into consideration generational toxicity will be needed to protect our future populations.

Keywords: epigenetics; generational toxicology; transgenerational.

Figure 1:

Schematic representation of the primary epigenetic factors and processes of non-coding RNA, DNA methylation, chromatin structure, histone modifications, and DNA structure presented. Modified from Nilsson et al. [1]

Figure 2:

Role of germ cell in epigenetic transgenerational inheritance. The exposure of an F0 generation gestating female promotes an epigenetic alteration in the germ cell programming of the F1 generation fetus. The F1 generation adult passes the germ cell epimutations to the zygote and early embryo to alter the embryonic stem cell epigenetics and transcriptome to impact all developing somatic cell epigenetics and transcriptomes to promote cell and tissue disease susceptibility. The altered germ cell epigenetics is then transgenerationally transmitted to subsequent generations. Modified from Nilsson et al. [1]

Figure 3:

Environmentally induced transgenerational epigenetic inheritance: schematic of environmental exposure and affected generations for both gestating female and adult male or female. The multigenerational direct exposures are indicated in contrast to the transgenerational generation having no direct exposure. Modified from Nilsson et al. [1]

Figure 4:

Environmentally induced epigenetic transgenerational inheritance. Various exposures and species investigated