Figure 6

Assessing if in utero exposure to ED results in transgenerationally inherited epigenetic aberration via the germline. (A) Normal epigenetic remodeling the male germline. MGC undergo normal erasure and normal re-establishment of DNA methylation, producing reprogrammed G1 (G1R) MGCs and G1R spermatozoa. (B) Hypothetical situation where a G1 embryo (two orange stars) exposed to ED during the de novo DNA methylation process results in aberrant reprogramming of G1R MGCs. The aberrant DNA methylation pattern may be maintained in G1R spermatozoa. Aberrant DNA methylation pattern of G1R sperm may harm G2 embryos (three blue stars), by germline epigenetic inheritance. The right panel shows a hypothetical situation in which in the absence of further ED exposure, an aberrant DNA pattern is inherited from the G1R spermatozoa. This aberration fails to be erased in G2 PGCs, and is carried further into G2R prospermatogonia and G2R spermatozoa, which have not been exposed directly or indirectly; thus, persistence of the aberration in these cells would constitute transgenerational epigenetic inheritance. Note that the DNA methylation patterns are simplified, for example, they do not take into account remodeling during the zygote-early embryo stages (green box). (C) Timing scheme of the genome-wide mapping studies. G1 fetuses were exposed in utero during the establishment phase (Exposure B), and G1R and G2R fetal MGCs and adult spermatozoa were collected for analysis.