News | Study Finds Age-Related Sperm Methylation Changes May Affect Offspring Neurodevelopment
A study found that as fathers age, methylation changes in sperm may affect offspring health, particularly neurodevelopment. Researchers from Julius-Maximilians-Universität, the Göttingen collaborative research center, and the Wiesbaden Fertility Center conducted the study, which was published in Aging. The authors suggest that age-related epigenetic methylation changes in sperm may be one mechanism contributing to neurodevelopmental disorders and other health conditions in offspring.
Background
Research increasingly finds that offspring of older fathers may face higher reproductive and health risks, especially involving neurodevelopment. Epigenetic changes in sperm, particularly methylation, have emerged as one possible explanation.
The study used reduced representation bisulfite sequencing (RRBS) to analyze 73 semen samples from men at a German fertility center. Significant age-related methylation changes appeared in sperm, with methylation decreasing in some regions and increasing in others.
Findings
Age-related methylation changes occurred mainly in gene regions, particularly genes involved in development and the nervous system. Of 1,565 differentially methylated regions studied (ageDMRs), 74% were located in gene regions, and 1,002 genes were significantly associated with age-related methylation changes.
Regions with lower methylation were generally closer to transcription start sites, while regions with higher methylation were more often in distal gene regions. The changes were not significantly associated with paternal body mass index (BMI), semen quality, or assisted reproductive technology (ART) outcomes, suggesting that age may affect sperm methylation independently of these factors.
Potential effects on offspring
The findings suggest that paternal age-related sperm methylation may alter offspring behavior and neurodevelopment. Analysis of 241 genes showing significant methylation changes across multiple studies found links to development, the nervous system, synapses, neurons, and other cellular components, supporting a potential role in neurodevelopment.
The methylation changes were not randomly distributed across the genome. Sperm methylation regions were notably enriched on chromosome 19, suggesting that this region may help regulate gene expression. Although high gene density and CpG-island content are preserved in corresponding primate chromosomes, no significant increase in age-related methylation changes was observed on chromosome 22 in the common marmoset.
Conclusion and outlook
The study further supports an association between age-related sperm methylation changes and susceptibility to conditions such as neurodevelopmental disorders in offspring. Further research is needed, but the findings offer a new perspective on how paternal age may affect offspring health.
The team plans to continue studying paternal age, sperm epigenetics, and offspring health, including the specific effects of methylation changes under different patterns such as prolonged exposure. This work may improve understanding of male reproductive health and inform future reproductive-health management.
News | Study Finds Age-Related Sperm Methylation Changes May Affect Offspring Neurodevelopment
News | Study Finds Age-Related Sperm Methylation Changes May Affect Offspring Neurodevelopment
A study found that as fathers age, methylation changes in sperm may affect offspring health, particularly neurodevelopment. Researchers from Julius-Maximilians-Universität, the Göttingen collaborative research center, and the Wiesbaden Fertility Center conducted the study, which was published in Aging. The authors suggest that age-related epigenetic methylation changes in sperm may be one mechanism contributing to neurodevelopmental disorders and other health conditions in offspring.
Background
Research increasingly finds that offspring of older fathers may face higher reproductive and health risks, especially involving neurodevelopment. Epigenetic changes in sperm, particularly methylation, have emerged as one possible explanation.
The study used reduced representation bisulfite sequencing (RRBS) to analyze 73 semen samples from men at a German fertility center. Significant age-related methylation changes appeared in sperm, with methylation decreasing in some regions and increasing in others.
Findings
Age-related methylation changes occurred mainly in gene regions, particularly genes involved in development and the nervous system. Of 1,565 differentially methylated regions studied (ageDMRs), 74% were located in gene regions, and 1,002 genes were significantly associated with age-related methylation changes.
Regions with lower methylation were generally closer to transcription start sites, while regions with higher methylation were more often in distal gene regions. The changes were not significantly associated with paternal body mass index (BMI), semen quality, or assisted reproductive technology (ART) outcomes, suggesting that age may affect sperm methylation independently of these factors.
Potential effects on offspring
The findings suggest that paternal age-related sperm methylation may alter offspring behavior and neurodevelopment. Analysis of 241 genes showing significant methylation changes across multiple studies found links to development, the nervous system, synapses, neurons, and other cellular components, supporting a potential role in neurodevelopment.
The methylation changes were not randomly distributed across the genome. Sperm methylation regions were notably enriched on chromosome 19, suggesting that this region may help regulate gene expression. Although high gene density and CpG-island content are preserved in corresponding primate chromosomes, no significant increase in age-related methylation changes was observed on chromosome 22 in the common marmoset.
Conclusion and outlook
The study further supports an association between age-related sperm methylation changes and susceptibility to conditions such as neurodevelopmental disorders in offspring. Further research is needed, but the findings offer a new perspective on how paternal age may affect offspring health.
The team plans to continue studying paternal age, sperm epigenetics, and offspring health, including the specific effects of methylation changes under different patterns such as prolonged exposure. This work may improve understanding of male reproductive health and inform future reproductive-health management.
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Compiled from online sources