Figure 1

Sex-specific transmission of exposure to environment to subsequent generations. Environmental factors - including nutrition, psychosocial stress, toxins, endocrine disruptors, tobacco, alcohol, microbiota – impact individual (F0) epigenetic landscapes hence gene pathways and networks in ways that differ between the sexes. For example maternal and paternal preconceptional exposures can modify gamete quality and be transmitted to the subsequent (F1) generation. Additionally consequences of maternal F0 exposure during pregnancy (stress, metabolism, diet, hormonal changes…) can be transmitted from the maternal to the fetal compartment via the placenta in a sex-specific manner and affect F1 tissue development. Programming of somatic tissues can lead to changes in long-term health outcomes in the first generation. Moreover, primordial germ cells, which develop and undergo reprogramming during fetal development, can also be affected by F0 maternal environment and contribute genetic and epigenetic information to the F2 generation. Maternal and paternal lineages affect the transmission of such influences differently. In particular, multigenerational exposure on the maternal lineage can be seen in the F0, F1 and F2 generations, and transgenerational phenotype would be observed in F3, whereas on the paternal lineage multigenerational exposure concerns F0 and F1, and transgenerational phenotype in F2 and F3 generations.