Figure 2. . Principles of intergenerational and transgenerational epigenetic inheritance.

(A) If a pregnant individual (F0) is exposed to an environmental perturbation, the offspring (F1; blue), and their germ cells (orange) that form the F2 generation (green) are also directly exposed, potentially resulting in intergenerational effects. The third generation (F3; purple) is the first generation that can demonstrate transgenerational epigenetic inheritance. (B) If an individual (F0) and their germ cells (orange) that will form the F1 generation (blue) are exposed directly to an environmental perturbation, the F2 offspring (green) are the first generation that can demonstrate transgenerational epigenetic inheritance. The same principles hold for animal models. (C) For a pregnant dam (F0), an exposure would impact her, her F1 offspring and the germline of her offspring (F2), and detection in the F1 and F2 generations would represent intergenerational epigenetic inheritance. Transgenerational epigenetic inheritance requires observing a detectable epigenetic change in the first unexposed generation (F3). (D) Exposure of a nonpregnant dam or sire (F0) affects that individual and their gametes (F1). Detection of an epigenetic change in the F1 generation would be intergenerational epigenetic inheritance, while detection in the F2 generation would be regarded as transgenerational epigenetic inheritance.