Are the Sins of the Father Passed On to the Child?
The Impact of Chronic Stress
Recent research led by Professor A. J. Hannan from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne indicates that a father’s chronic stress can indeed affect his children’s mental health. The findings, published in Molecular Psychiatry, reveal that stress hormones can alter sperm, leading to changes that may increase the risk of anxiety and depression in offspring.
Understanding Epigenetic Inheritance
Previous studies have established that parental experiences can leave a genetic imprint on their children, a process known as epigenetic inheritance. This means that experiences can modify genes in ways that are passed down to future generations. The research team had earlier discovered that stress-related changes in small non-coding RNAs in sperm could heighten anxiety in male offspring. In this latest study, they focused on long non-coding RNAs (lncRNAs) to further explore how stress effects might be transmitted.
Professor Hannan stated, “We published a study eight years ago showing that increased stress hormones caused changes to small non-coding RNAs in sperm of father mice, and changes in anxiety and social behavior in their offspring. We therefore wanted to study long non-coding RNAs and investigate whether these changes in sperm RNAs could contribute to changes in offspring brain and behavior.”
The Role of RNA in Genetic Communication
RNA functions as a messenger, relaying instructions from DNA to control protein production, essential for body functions. In this context, DNA acts as the blueprint, while RNA provides the detailed instructions for building specific bodily components. The study aimed to determine if stress alters these instructions in sperm, which could subsequently affect the offspring’s brain development.
While both small and long non-coding RNAs do not encode proteins, they serve different functions. Small non-coding RNAs primarily regulate gene expression, whereas long non-coding RNAs are longer and have diverse roles, including influencing DNA structure and modifying other RNA molecules.
Methodology: Investigating Stress Transmission
To examine the effects of stress, researchers utilized two groups of male mice. One group received corticosterone, a stress hormone, in their drinking water for four weeks to simulate chronic stress, while the control group was given regular water. After the stress treatment, the researchers analyzed the sperm for changes in long non-coding RNAs using a technique called CaptureSeq.
To assess the impact of these changes, the team injected the altered RNAs into fertilized mouse eggs, which were then implanted into female mice to produce offspring. Behavioral tests were conducted on the offspring to evaluate anxiety, depression, social dominance, and attractiveness to potential mates. These tests included maze navigation and light-dark box assessments.
Findings: Behavioral Changes in Offspring
The analysis revealed significant changes in the long non-coding RNA profiles of sperm due to stress. Out of 7,552 long non-coding RNAs, 2,382 were altered in stressed mice, with 772 increased and 1,610 decreased. Notably, these changes affected specific long non-coding RNAs known to influence brain development.
Offspring that received the altered long non-coding RNAs exhibited marked behavioral differences. Males demonstrated increased anxiety, spending more time in the illuminated areas of the light-dark box, and showed heightened signs of depression, such as quicker immobility in swim tests. Additionally, these offspring were larger than those conceived naturally, indicating that long non-coding RNAs can also influence physical development.
Professor Hannan expressed surprise at the extent of changes in long non-coding RNAs due to heightened stress hormone levels, emphasizing the relevance of these findings to depression and anxiety disorders. He noted the importance of further research to determine whether similar changes occur in human sperm and their potential contribution to brain disorders in future generations.
References
1. Hoffmann, L.B. et al. (2023) ‘Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours’, Molecular Psychiatry, 29(3), pp. 590–601. doi:10.1038/s41380-023-02350-2.
2. Arzate-Mejía RG, Mansuy IM. Epigenetic Inheritance: Impact for Biology and Society-recent progress, current questions and future challenges. Environ Epigenet. 2022 Nov 5;8(1):dvac021. doi: 10.1093/eep/dvac021. PMID: 36589550; PMCID: PMC9790978.
3. Short, A.K. et al. (2016) ‘Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring’, Translational Psychiatry, 6(6). doi:10.1038/tp.2016.109.
4. Dolan, E.W. (2024) Chronic stress can alter genetic material in sperm, leading to changes in offspring behavior, PsyPost. Available at: https://www.psypost.org/chronic-stress-can-alter-genetic-material-in-sperm-leading-to-changes-in-offspring-behavior/# (Accessed: 14 October 2024).
5. Ribonucleic acid (RNA) (no date) Genome.gov. Available at: https://www.genome.gov/genetics-glossary/RNA-Ribonucleic-Acid (Accessed: 14 October 2024).
6. Li X, Peng J, Yi C. The epitranscriptome of small non-coding RNAs. Noncoding RNA Res. 2021 Oct 26;6(4):167-173. doi: 10.1016/j.ncrna.2021.10.002. PMID: 34820590; PMCID: PMC8581453.
7. Mattick, J.S. et al. (2023) ‘Long non-coding RNAs: Definitions, functions, challenges and recommendations’, Nature Reviews Molecular Cell Biology, 24(6), pp. 430–447. doi:10.1038/s41580-022-00566-8.