Fig. 2

Hypothesis on the interplay between genetics and epigenetics in response to ancestral exposure to EDCs. Direct exposure to F1 (through pregnancy of F0 or directly in the life course of F1) causes a “temporal” or a “persistent” epigenetic effect (represented by a black dot), or no effect at all. A temporal effect relates to an intergenerational transmission of the exposure, and a persistent effect refers to a transgenerational phenomenon, as earlier described by Skinner [32]. We here suggest that a genomic variation or a polymorphism in the exposed generation (represented by a, b, and c) plays a role in “losing” or “maintaining” the epigenetic effect in future generations. Partly based on our interpretation of reports discussed in this review, we believe that the interplay between environmentally induced epigenetic changes (also called “primary epimutations” by McCarrey et al. [70]) and (pre-existing) individual genetic characteristics (as we here hypothesize) may induce structural or regulatory changes at the level of the DNA in F2 germ cells, resulting in failure to erase past messages and—at the same time- inducing alterations in the ability to control genomic integrity. We suggest that future studies on transgenerational effects scrutinize potential synergistic mechanisms where both features—a genetic variability and an exposure-induced epigenetic effect—coactively cause a persistent modification in future generations. A triangle represents yet unknown mechanism involved. Because these effects are indirect consequences of an earlier exposure, it can be interpreted as an adaptation to the new environment. This novel scenario could also contribute to the (unexplained) acceleration in evolution and speciation, earlier discussed in the context of dietary exposures [23]