Figure 2.

Environmental exposures induce dynamic methylome changes during post-zygotic and primordial germ cell (PGC) development resulting in inter- and trans-generational inheritance. The first phase is the rapid erasure of methylation marks in the male (blue line) and female (purple line) germline, that occurs shortly after fertilization. It is followed by the establishment of a new methylome in the implanting blastocyst. Progressive chromatin restriction gives rise to differentiated tissues. Environmental agents induce unique gene promoter methylation changes in different tissues. The second phase launched during sexual differentiation through birth establishes the sperm- and oocyte- specific heritable marks. Ovarian reserve (OvR) is determined at birth while male germ cells are replenished throughout life. Inter-generational transmission (light grey line) largely involves the first phase while transgenerational inheritance (dark grey line) requires both phases.