Detailed profiles of histone modification in male germ line cells of the young and aged mice

Human epidemiological studies have shown paternal aging as one of the risks for neurodevelopmental disorders such as autism in offspring. This is modeled in rodents; offspring derived from aged fathers showed behavioral abnormalities. Since we have noticed that some of the behavior traits are not transmitted to the second generation, we are focusing on epigenetic changes that can influence offspring developmental programs. In this study, we qualitatively and semi-quantitatively evaluated histone modification patterns in male germ line cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months) and aged (12 months) old mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, H3K9me3 was decreased in the male germ line cells in aged testes, while H3K27me2/3 were increased. The intensity of H3K27ac that activates gene expression was relatively low in aged testes. Interestingly, H3K27ac was detected in putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germ line cells in the aged testis. H3K79me3 was contrastingly increased and accumulated on the sex chromosomes at M-phase spermatocytes. Therefore, aging induced alterations in the amount of histone modifications, of which patterns were different in individual histone modifications. Moreover, histone modification seems to be differentially regulated by aging on the sex chromosomes and on others. These findings would help elucidate epigenetic mechanisms underlying influence of paternal aging on offspring9s development.