Childhood stress impacts epigenetic profile of sperm and brain development

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."

Professor Noora Kotaja, 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.