Environmentally induced epigenetic transgenerational inheritance of disease

Abstract

Ancestral environmental exposures such as toxicants, abnormal nutrition or stress can promote the epigenetic transgenerational inheritance of disease and phenotypic variation. These environmental factors induce the epigenetic reprogramming of the germline (sperm and egg). The germline epimutations can in turn increase disease susceptibility of subsequent generations of the exposed ancestors. A variety of environmental factors, species and exposure specificity of this induced epigenetic transgenerational inheritance of disease is discussed with a consideration of generational toxicology. The molecular mechanisms and processes involved in the ability of these inherited epimutations to increase disease susceptibility are discussed. In addition to altered disease susceptibility, the potential impact of the epigenetic inheritance on phenotypic variation and evolution is considered. Observations suggest environmentally induced epigenetic transgenerational inheritance of disease is a critical aspect of disease etiology, toxicology and evolution that needs to be considered.

Keywords: disease etiology; epigenetics; evolution; non-genetic inheritance; review; transgenerational.

Figure 1:

epigenetic mechanisms and processes (marks). Modified from [122]

Figure 2:

epigenetic and genetic cascade of events involved in development. Cascade of genetic and epigenetic stages interacting to promote differentiated cells. The critical window of exposure allows environmental factors to alter the epigenetic cascade to obtain a modified differentiated site and to cause altered transcriptomes to increase disease susceptibility and phenotypic variation. Modified from [3]

Figure 3:

environmentally induced transgenerational epigenetic inheritance. Schematic of multigenerational versus transgenerational environmental exposures. Modified from [31]

Figure 4:

environmentally induced epigenetic transgenerational inheritance. Various exposures and species investigated

Figure 5:

epigenetic reprogramming during primordial germ cell development at gonadal sex determination and following fertilization in the early embryo. Modified from [94]