Abstract
Childhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual.
Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven
epigenetic changes in the germ line. Here we investigated the associated between early life stress on the epigenome of sperm in
humans with history of CME. We measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped
sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by
reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a
(nested) case-control study, high-TADS (TADS ≥ 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS ≤ 10,
n = 30 for DNAme and n = 16 for small RNA-seq). We identified 3 genomic regions with differential methylation between low and
high-TADS and 68 tRNA-derived small RNAs (tsRNAs) and miRNAs with different levels in males with high CME (False discovery rate,
FDR corrected p < 0.05). Of potential interest, we identified differential expression of miRNA hsa-mir-34c-5p and differential
methylation levels near the CRTC1 and GBX2 genes, which are documented to control brain development. Our results provide
further evidence that early life stress influences the paternal germline epigenome and supports a possible effect in modulating the
development of the central nervous system of the next generation.
Molecular Psychiatry; https://doi.org/10.1038/s41380-024-02872-3
The article investigates the association between childhood maltreatment exposure (CME) and specific epigenetic changes in sperm. It examines how early-life psychological stress might alter the paternal germline epigenome, potentially affecting the development of the next generation.
Key Findings:
- Epigenetic Changes in Sperm: The study identifies specific modifications in DNA methylation and small non-coding RNA (sncRNA) expression in the sperm of individuals with a history of CME.
- Differential Gene Expression: Changes in miRNA (especially hsa-mir-34c-5p) and DNA methylation levels near genes (CRTC1 and GBX2) linked to brain development.
- Potential Intergenerational Effects: The findings suggest that these epigenetic modifications might influence the central nervous system development of offspring.
The study uses data from the FinnBrain Birth Cohort Study and applies small RNA sequencing (small RNA-seq) and reduced-representation bisulfite sequencing (RRBS-seq) to analyze sperm samples from fathers with high and low CME scores.
Preventive Measures
Circumventing the effects of childhood maltreatment exposure (CME) on the sperm epigenome requires a combination of lifestyle interventions, psychological support, and possibly medical strategies to promote sperm health and reduce the transmission of adverse effects to offspring. Here are some potential ways to mitigate these effects:
1. Lifestyle Interventions for Epigenetic Reprogramming
- Diet and Nutrition:
- A diet rich in antioxidants, folate, and omega-3 fatty acids (found in fish, nuts, fruits, and vegetables) may help restore healthy sperm DNA methylation patterns.
- Methyl donors such as folic acid, choline, and vitamin B12 can support proper DNA methylation.
- Exercise:
- Regular moderate exercise has been shown to reverse stress-induced epigenetic changes and improve sperm quality.
- Avoiding Toxins:
- Reducing exposure to alcohol, tobacco, and environmental pollutants can help prevent further epigenetic damage in sperm.
- Sperm Cryopreservation:
- If a person has been exposed to CME and is concerned about passing on epigenetic changes, they may consider freezing sperm at an early age, before additional stressors impact sperm quality.
2. Psychological and Stress-Reduction Strategies
- Trauma Therapy and Counseling:
- Cognitive Behavioral Therapy (CBT), psychotherapy, or trauma-focused therapy can help address long-term effects of CME and may reduce stress-related epigenetic alterations.
- Mindfulness and Stress Management:
- Meditation, deep breathing, and yoga can lower cortisol levels, which influence epigenetic markers in sperm.
- Social Support and Healthy Relationships:
- Positive social interactions and stable relationships have been linked to better mental health outcomes, which may indirectly benefit epigenetic programming.
3. Potential Medical and Epigenetic Interventions
- Pharmacological Approaches:
- Emerging research suggests that epigenetic drugs (such as HDAC inhibitors or DNA methyltransferase inhibitors) may help reset DNA methylation patterns. However, this is still experimental.
- Assisted Reproductive Technologies (ART):
- Some studies suggest that pre-implantation epigenetic screening may help select embryos with the most favorable epigenetic profiles.
- Sperm Selection Techniques:
- Advanced sperm selection methods (e.g., microfluidic sperm sorting) might help choose healthier sperm with lower levels of epigenetic damage.
4. Transgenerational Strategies (for Offspring)
If an individual with CME has already had children, efforts should focus on:
- Providing a nurturing and stress-free early environment for their children.
- Encouraging secure parent-child attachment, as early childhood experiences can shape gene expression in the next generation.
Conclusion
While epigenetic changes caused by CME can persist, lifestyle modifications, mental health support, and possible medical interventions offer promising ways to mitigate the effects and promote healthier sperm and offspring development.