Summary: Childhood stress may leave lasting marks on sperm, altering epigenetic profiles and potentially influencing brain development in offspring. Researchers found that men with high levels of childhood maltreatment had changes in DNA methylation and non-coding RNA levels in their sperm.
These epigenetic changes could mediate how early life stress impacts the next generation, highlighting the potential for intergenerational effects. While the study demonstrates significant associations, further research is needed to confirm the role of epigenetic inheritance in humans.
Key Facts
- Sperm Epigenetic Changes: Childhood maltreatment altered DNA methylation and non-coding RNA in sperm.
- Brain Development Links: These changes are associated with brain development in offspring.
- Intergenerational Impact: Findings suggest early life stress may influence future generations via epigenetics.
Source: University of Turku
Childhood stress can impact the epigenetic profile of sperm. These results may also have practical implications for future generations through epigenetic inheritance, as many of the observed epigenetic associations are related to brain development.
This ground-breaking discovery has been made in the FinnBrain study at the University of Turku, Finland, in collaboration with researchers from the University of Copenhagen, Denmark.
Epigenetic inheritance refers to the transmission of information on acquired conditions to the next generation without it being encoded in the DNA sequence. Changes caused by the environment may therefore be passed on from generation to generation through gametes.
Researchers from the FinnBrain study at the University of Turku have previously found an association between paternal early life stress exposure and the child’s brain development.
In a recent study, childhood maltreatment was found to be associated with several sperm epigenetic characteristics that may mediate the effects on offspring brain development, including expression levels of the non-coding RNA molecule hsa-miR-34c-5p and methylation of the CRTC1 and GBX2 genes.
“Next, we want to study childhood maltreatment, epigenome of sperm, and offspring characteristics together. Demonstrating epigenetic inheritance in humans would rewrite the rules of inheritance, which highlights the need for further research,” says Jetro Tuulari, who is the first author of the article.
Although all cells in the body have the same genes and DNA, they have distinct epigenetic profiles, which determines their different appearance and function. Epigenetic regulation thus enables differences in the cells of the brain, muscles, and skin by silencing and activating genes.
Epigenetic changes in gametes have a special role, as they can also affect subsequent generations via epigenetic inheritance.
“Epigenetic inheritance via sperm epigenome is a fascinating research topic and the mechanisms involved are under active investigation in my research group.
“There are currently several projects studying the phenomenon in both animal models and humans. This study was the largest and most comprehensive human study conducted so far,” says Professor Noora Kotaja, a senior researcher in the study.
The study found lower levels of sperm DNA methylation in three DNA regions and changed levels of several small non-coding RNA molecules in men with high levels of childhood maltreatment. They were compared with men who had few experiences of maltreatment, as measured by questionnaires.
Altogether 55 middle-aged men took part in the study. In the statistical modelling, many other health factors such as the respondent’s age, weight and smoking were controlled for.
“The FinnBrain cohort and other multi-generational data from the Centre for Population Research will enable other similar high-quality studies on human epigenetic inheritance. However, the inheritance of these findings has not yet been proven, so further research is needed,” says Professor Emeritus Hasse Karlsson, who initiated the FinnBrain study.
Launched in 2010, FinnBrain is a birth cohort study of the University of Turku involving over 4,000 families and aiming at exploring environmental and genetic factors influencing the development of a child. The parent study of the cohort is also a key part of the project’s research, and this sub-study focuses on paternal health in the cohort.
About this epigenetics research news
Author: Tuomas Koivula
Source: University of Turku
Contact: Tuomas Koivula – University of Turku
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm” by Jetro J. Tuulari et al. Molecular Psychiatry
Abstract
Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm
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.
