Developmental origins of epigenetic transgenerational inheritance

Abstract

Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective.

Keywords: critical windows; disease; epigenetic; generational; transgenerational.

Figure 1

epigenetic (DNA methylation) programming in the germline during various developmental periods. The green line is the male germline developmental pattern and blue line the female germline developmental pattern (modified from [ 1 ])

Figure 2

epigenetic and genetic cascade of events (arrows) from a stem cell state to a differentiated adult state involved in development. A normal or environmentally modified state promotes genome alterations associated with an increase susceptibility for disease and phenotypic variation. The critical window of early development is when environmental factors have the ability to alter the epigenome (modified from [ 71 ])

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 without direct exposure (modified from [ 97 ])