The authors focused on the difference in epigenetic states within a regulatory region of Pparg in livers derived from normal and injured offspring. Consistent with adaptive changes in the expression of Pparg, they detected hypomethylation in the regulatory region of Pparg in livers at peak fibrosis from injured offspring. According to germ plasm theory as proposed by Weisman, transmission of a father’s epigenetic information to offspring is mediated only by the sperm. Therefore, the authors verified the possibility that liver fibrosis induces changes in DNA methylation of Pparg in sperm derived from injured male rats. However, they could not detect RAD001 cell line DNA methylation

of Pparg in the sperm. Therefore, they focused on other epigenetic marks, histone variants H2A.Z and H3K27me3, which are reported to be mutually exclusive with DNA methylation. Both the distribution of H2A.Z and the modification of H3K27me3 on Pparg were enriched Olaparib in sperm derived from both CCl4-treated and bile duct-ligated male rats compared to controls. They propose that the enrichment of H2A.Z and H3K27me3 on Pparg in sperm is a form of epigenetic memory for the inheritance of adaptive information against a liver wound-healing response to offspring. Epigenetic information in germline cells is extensively reprogrammed at several stages, spermatogenesis, early embryo, and primordial germ cells (PGCs), the source of both oocytes and

spermatozoa. Although canonical histones are largely exchanged for protamine, a small basic protein that is involved in the packaging of sperm DNA during spermatogenesis, about 4% of the haploid genome retains nucleosomes consisting of H2A.Z and H3K27me3.7 Furthermore, it has been shown that genome-wide epigenetic modifications, medchemexpress including DNA methylation and H3K9me2, are erased in early embryo and/or PGCs, while the genome-wide H3K27me3 erasure is not observed in germ cell development.8 These findings led me to consider that epigenetic information consisting of H3K27me3 is relatively more transmittable to the next generation, compared to DNA methylation and H3K9me2. Consistent with my consideration,

another study about intergenerational transmission of epigenetic information has also suggested that changes in H3K27me3 modification in sperm by the intake of a low-protein diet affect offspring behavior.9 Recently, several reports have shown that changes in epigenetic information induced by environmental cues are inherited through the germline.9, 10 However, the precise route of transmission of epigenetic information from father to offspring has been largely unknown. The latest finding, demonstrated in this study, is that serum acts as a carrier of the characteristics, acquired due to environmental effects, to the sperm. The transfer of serum derived from injured male rats to uninjured male rats gave rise to enrichment of H2A.