A) Crossing scheme used in rodent studies to generate genetically wild type progeny from a mutant ancestor. Color of mouse denotes phenotype (blue are wild type and red are mutant). Note that in many instances presented in the review, the phenotype of the F1 heterozygotes is unknown.
B)Crossing scheme used in worm studies to generate genetically wild type progeny from a mutant ancestor. The F1 generation arises from mating between a hermaphrodite and male. The F2 generation arises from the self-fertilization of F1 hermaphrodites. Color of worm denotes phenotype (blue are wild type and red are mutant). Note that in many instances presented here, the phenotype of the F1 heterozygotes is unknown.

A) Strategy used to generate progeny from a paternal ancestor subject to an environmental perturbation. This scheme minimizes maternal effects in organisms that require significant maternal care during development. Blue: normal phenotype. Green: altered phenotype resulting from a perturbation to the ancestral environment.
B)Scheme used to generate progeny from a maternal ancestor subject to an environmental perturbation. This scheme allows for the study of transgenerational effects induced by an initial change in maternal environment, but minimizes cryptic maternal effects. Blue: normal phenotype. Green: altered phenotype resulting from a perturbation to the ancestral environment.

Alterations to the parental genome (aqua arrow) or environmental stimuli (green arrow) could trigger epigenetic changes in the germline of the organism that could be transmitted to the next generation. Such epigenetic changes could possibly be relayed or amplified in the germline of subsequent generations, and persist for several generations. Eventually, epigenetic changes would be reset to a basal state. So far, the epigenetic mechanisms that have been described include changes to chromatin (histone marks, DNA methylation) and changes to non-coding RNAs, in particular those involving the nuclear RNAi pathway. An amplification loop could be initiated by alteration in chromatin marks (e.g. H3K9me3) at a genomic locus, followed by the generation of non-coding RNAs at this particular locus, which would then be transmitted via the germline, and in turn guide H3K9me3 deposition at that same genomic locus in the germline of the next generation. In grey are additional potential mechanisms that remain to be investigated ().