ArticleInternational journal of molecular sciences2025
rDNA Copy Number Variation and Methylation in Human and Mouse Sperm.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Pathogenic germline variants in BRCA1/2 are associated with a decreased number of hypomethylated rDNA copies.Breast cancer research : BCR · 2026Article
- Sperm rDNA Copy Number and Methylation Are Associated with Male-Factor Infertility.International journal of molecular sciences · 2025Article
- Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
In this study, droplet digital PCR and deep bisulfite sequencing were used to study the absolute and active rDNA copy number (CN) and the effect of paternal age on human and mouse sperm. The absolute CN ranged from 98 to 404 (219 ± 47) in human and from 98 to 177 (133 ± 14) in mouse sperm. Methylation of the human upstream control element/core promoter (UCE/CP) region and the 5' external transcribed spacer, as well as that of the mouse CP, the spacer promoter, and 28S rDNA, significantly increased with donor age and absolute CN. Overall, rDNA hypomethylation was much more pronounced in mouse sperm, with 101.7 ± 11.4 copies showing a completely (0%) unmethylated and 11.3 ± 2.8 (8.5%) a slightly methylated (1-10%) CP region, compared to humans with 25.7 ± 9.5 (12%) completely unmethylated and 83.0 ± 19.8 slightly methylated UCE/CP regions. Although the absolute CN was much higher in human sperm, the number of copies with a hypomethylated (0-10%) promoter was comparable in humans (108.7 ± 28.3) and mice (113.0 ± 12.2). However, in mice, the majority (77%) of all copies were completely unmethylated, whereas in humans a high percentage (38%) showed one or two single CpG methylation errors. These different germline methylation dynamics may be due to species differences in reproductive strategies and lifespan. Complete demethylation of the sperm rDNA promoter in mice may be essential for embryonic genome activation, which already occurs at the 2-cell stage in mice and at the 4-8-cell stage in humans. The paternal age effect has been conserved between humans and mice with some notable differences. In humans, the number of hypomethylated (0-10%) copies decreased with age, whereas in mice only the completely unmethylated copies decreased with age. The number of methylated rDNA copies (>1% in mice and >10% in humans) significantly increased with age.
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