FIGURE 2:

Theoretical biological pathways underlying multi/transgenerational inheritance: 1) Additive model of germline impacts downstream of drug exposure, wherein changes in reproductive functioning, germline integrity, and/or germline epigenome additively mediate multi/transgenerational inheritance; 2) Sequential model of germline impacts downstream of drug exposure, wherein changes in reproductive functioning cause altered germline integrity, which then triggers germline epigenomic modifications that mediate multi/transgenerational inheritance; 3) & 4) Alternative sequential models, wherein impacts of drug exposure on one or more, but not all, of the discussed factors in sequence are sufficient to produce multi/transgenerational phenotypes; 5) and 6) Pathways depicting a single independent mediator of multi/transgenerational inheritance in drug exposure models.