Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.
Level 3 - non-randomized controlled study
Longitudinal within-subject observational cohort study comparing paired human sperm samples collected years apart.
PubMed 25010591 · doi:10.1371/journal.pgen.1004458
What was done
The authors used a DNA methylation array to assess changes in mature human sperm methylomes from 17 fertile donors. Each donor provided two sperm samples collected 9 to 19 years apart, enabling a longitudinal within-individual comparison. A representative subset of identified alterations was subsequently tested for confirmation in an independent cohort.
What was found
Advancing age was associated with 139 significantly and consistently hypomethylated regions and 8 significantly hypermethylated regions. These alterations mapped to 117 genes (promoter or gene body), with a subset located at genes previously associated with schizophrenia and bipolar disorder. Specific numerical effect sizes, significance values, and the size of the replication cohort were not reported in the abstract.
Why it matters
This work provides within-individual longitudinal evidence that human sperm undergoes locus-specific DNA methylation changes with age. These alterations point to potential epigenetic mechanisms that might underlie epidemiological associations between paternal age and offspring disease risk.
Limits
The discovery cohort was very small (n = 17), and the sample size and details of the independent replication cohort were not provided in the abstract. The study did not measure epigenetic persistence through fertilization or clinical outcomes in offspring, so causality between these alterations and offspring disease remains unproven.
Cited by
- supports The sperm methylome changes with age, differing between 50-year-old and 20-year-old men.