title: Genome-Scale Assessment of Age-Related DNA Methylation Changes in Mouse Spermatozoa.
abstract: DNA methylation plays important roles in the production and functioning of spermatozoa. Recent studies have suggested that DNA methylation patterns in spermatozoa can change with age, but the regions susceptible to age-related methylation changes remain to be fully elucidated. In this study, we conducted genome-scale DNA methylation profiling of spermatozoa obtained from C57BL/6N mice at 8 weeks (8w), 18 weeks (18w) and 17 months of age (17m). There was no substantial difference in the global DNA methylation patterns between 18w and 17m samples except for a slight increase of methylation levels in long interspersed nuclear elements in the 17m samples. We found that maternally methylated imprinting control regions (mICRs) and spermatogenesis-related gene promoters had 5-10% higher methylation levels in 8w samples than in 18w or 17m samples. Analysis of individual sequence reads suggested that these regions were fully methylated (80-100%) in a subset of 8w spermatozoa. These regions are also known to be highly methylated in a subset of postnatal spermatogonia, which might be the source of the increased DNA methylation in 8w spermatozoa. Another possible source was contamination by somatic cells. Although we carefully purified the spermatozoa, it was difficult to completely exclude the possibility of somatic cell contamination. Further studies are needed to clarify the source of the small increase in DNA methylation in the 8w samples. Overall, our findings suggest that DNA methylation patterns in mouse spermatozoa are relatively stable throughout reproductive life.
authors.affiliation: Department of Informative Genetics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.|Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Informative Genetics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okae
authors.affiliation: Department of Informative Genetics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hiura
authors.affiliation: Department of Informative Genetics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Hatsune
authors.initials: H
authors.lastname: Chiba
authors.affiliation: Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shirakata
authors.affiliation: Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Hara
authors.affiliation: Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanemura
authors.affiliation: Department of Informative Genetics, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arima
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019175:DNA Methylation / Q000502:physiology*; D018392:Genomic Imprinting / Q000502:physiology*; D008297:Male; D051379:Mice; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*