Epigenetic transgenerational actions of environmental factors in disease etiology

Abstract

The ability of environmental factors to promote a phenotype or disease state not only in the individual exposed but also in subsequent progeny for successive generations is termed transgenerational inheritance. The majority of environmental factors such as nutrition or toxicants such as endocrine disruptors do not promote genetic mutations or alterations in DNA sequence. However, these factors do have the capacity to alter the epigenome. Epimutations in the germline that become permanently programmed can allow transmission of epigenetic transgenerational phenotypes. This review provides an overview of the epigenetics and biology of how environmental factors can promote transgenerational phenotypes and disease.

Figure 1. Proposed etiology of how the environmental impacts on disease

The cascade of molecular and physiological processes following an environmental exposure to promote disease is shown.

Figure 2. Role of the germ line in epigenetic transgenerational inheritance

(i) An environmental factor acts on the F0 generation gestating female to influence (ii) the developing F1 generation fetus and alter gonadal development to reprogram the primordial germ cell DNA methylation. (iii) This altered DNA methylation in the germ line becomes permanently programmed similar to an imprinted-like gene and is transferred through the germ line to subsequent generations. The embryo generated from this germ line starts with an altered epigenome that (iv) affects developing somatic cells and tissues to have an altered transcriptome. This altered somatic cell transcriptome can then promote adult onset disease associated with the transgenerational phenotype.