September 9, 2014
Correspondence: Michael K Skinner skinner@wsu.edu
Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman 99164-4236, WA, USA
More about author: skinner.wsu.edu/piskinner.html
BMC Medicine 2014, 12:153 doi:10.1186/s12916-014-0153-y
Background
The ability of environmental factors, such as stress [1], to promote the epigenetic transgenerational inheritance of disease and phenotypic variation has now been established in a number of organisms ranging from plants to humans, with a variety of environmental exposures [2]. One of the first studies found that environmental toxicants such as fungicides and pesticides promoted epigenetic transgenerational inheritance of reproductive disease [3]. Subsequently a large number of different types of toxicants (plastics, hydrocarbons, dioxin, biocides, dichlorodiphenyltrichloroethane (DDT)) have been shown to promote the transgenerational inheritance of disease [4] from obesity to cancer [5] (Table 1). Other critical environmental factors found to promote transgenerational disease are nutritional abnormalities such as caloric restriction or high fat diets [6]. In species such as insects and plants both drought and temperature have also been shown to be critical environmental factors [7],[8] (Table 1). Therefore, a large number of environmental factors have been shown to promote the epigenetic transgenerational inheritance of disease or phenotypic variation in a variety of different species, including humans [9]. This environmentally induced form of non-genetic inheritance will have a significant impact on disease etiology [2],[10] and areas of biology such as evolution [11].
Epigenetic transgenerational inheritance is defined as ‘the germline (egg or sperm) transmission of epigenetic information between generations in the absence of any environmental exposure’ [10]. Direct environmental exposure does not involve a generational phenotype, only direct toxicity or physiological effects of the individual exposed [2]. As previously described [2],[32], the exposure of an individual any time during development (F0 generation) results in the exposure of that individual and the germline (sperm or egg) that will generate the next generation (F1 generation) (Figure 1). The exposure of a gestating female exposed the F0 generation female, F1 generation fetus and germline that will generate the F2 generation (Figure 1). The ability of an exposure to act on multiple generations is termed a multigenerational exposure [32]. Where direct exposure is involved, no transgenerational effects are observed. Unfortunately, many studies have misused the term transgenerational to refer to multigenerational exposure effects. By contrast, if studies are extending to generations with no direct environmental exposure then observed effects can be considered transgenerational because the germline is the only cell type able to transmit epigenetic information generationally (Figure 1).
Epigenetics is defined as ‘molecular factors/processes around DNA that regulates genome activity independent of DNA, and that are mitotically stable’ [10]. The types of molecular processes involved are DNA methylation, histone modifications, chromatin structure, and non-coding RNA (ncRNA). The best characterized epigenetic factor to be involved in germline transmission of epigenetic information is DNA methylation. An example is imprinted genes that mediate paternal or maternal allelic transmission of specific DNA methylation patterns [33]. A number of studies have shown that environmentally induced epigenetic transgenerational inheritance involves altered germline DNA methylation [4],[34]. More recently ncRNA has been suggested as an additional mechanism in germline transmission of epigenetic information [35]. Histone modifications have also been suggested in a variety of organisms [36]. Although DNA methylation has a critical role in fetal germline development and early embryonic development [37], all the epigenetic processes will likely be involved and have unique functions in regulating development [10]. Further studies regarding the role of all epigenetic processes in environmentally induced epigenetic transgenerational inheritance are required.
# The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/12/153
Image source: http://learn.genetics.utah.edu/content/epigenetics/inheritance/
