Endocrine disruptor induction of epigenetic transgenerational inheritance of disease

Abstract

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease.

Keywords: DNA methylation; Environment; Epimutations; Evolutionary biology; Review; Toxicants.

Figure 1

Epigenetic and genetic cascade of events involved in development. Modified from [4].

Figure 2

Environmentally induced epigenetic transgenerational inheritance through male germline. Exposure of the F0 generation gestating female, F1 generation fetus, and germline within the F1 generation fetus that will generate the F2 generation. Therefore, the F3 generation is the first transgenerational generation not directly exposed. Modified from [24].

Figure 3

Ancestral exposure specific epimutation biomarkers. Transgenerational F3 generation sperm differential DNA methylation regions (epimutations) with the total listed next to exposure in brackets and Venn diagram showing overlap between the exposure epimutation. Modified from [30].

Figure 4

Role of germline in epigenetic transgenerational inheritance. Summary of environmentally induced epigenetic reprogramming of primordial germ cells that leads to the germline transmission of epimutations resulting in all somatic cells having an altered transcriptome that results in disease susceptibility. Modified from [5].

Figure 5

Schematic of environmental effects of epigenetics promoting disease etiology or phenotypic variation to influence evolution.