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.
Highlights
Spermatozoa develop from male primordial germ cells (PGCs)
We found that the mean methylation levels of long interspersed nuclear elements (LINEs) gradually increased with age (80.0% at 8w, 82.0% at 18w and 83.1% at 17m)
We found that methylated imprinting control regions (mICRs) and spermatogenesis-related gene promoters had 5–10% higher methylation levels in spermatozoa samples from 8w mice than in those from 18w and 17m mice
Summary
Spermatozoa develop from male primordial germ cells (PGCs). PGCs arise from proximal epiblast cells and migrate to the genital ridges, where they differentiate into mitotically arrested prospermatogonia (PSG) [1]. PSG resume proliferation and give rise to spermatogonial stem cells (SSCs), which ensure continual production of spermatozoa throughout life. Age-Related DNA Methylation Changes in Mouse Spermatozoa the Japan Agency for Medical Research and Development (AMED) (TA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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