Sperm may carry effects of childhood maltreatment to future generations

Men who experienced abuse or neglect in childhood show distinct changes in the molecular makeup of their sperm, according to new research published in Molecular Psychiatry. The study found that men with high levels of childhood maltreatment had altered patterns in small RNA molecules and DNA methylation within their sperm. These biological markers are thought to play an important role in gene regulation and development. The findings offer new clues into how early life stress may impact not only individuals themselves, but potentially their future children through a process known as epigenetic inheritance.

Epigenetic inheritance refers to the passing of biological information from one generation to the next that does not involve changes to the DNA sequence itself. Instead, it involves chemical modifications—such as DNA methylation or changes in small RNA molecules—that can affect how genes are turned on or off.

The new study was launched to explore whether childhood stress might leave a lasting biological imprint that goes beyond the person directly affected. While previous animal studies had shown that stress experienced by males early in life could change sperm and affect the behavior or health of their offspring, similar evidence in humans was still very limited. The idea that a father’s childhood experiences could be biologically encoded in his sperm and potentially passed on through epigenetic mechanisms intrigued the researchers, especially since sperm contributes half of the genetic and regulatory material at conception.

Their motivation was further strengthened by earlier work showing associations between paternal childhood adversity and structural changes in the brains of newborns. This finding was surprising, as it suggested a link between a father’s early life and the development of a child’s brain. That observation raised a critical question: how could a father’s early psychological stress affect a child he hasn’t yet conceived? The team hypothesized that sperm could be a potential pathway through which early experiences are transmitted.

“We have published a prior study that found associations between paternal childhood maltreatment exposure and neonatal brain white matter. This is striking as the fathers do not have direct influence on the developing fetus during pregnancy. This sparked my interest towards this line of research,” said study author Jetro J. Tuulari, the director of Turku Brain and Mind Center at the University of Turku.

To carry out the study, the researchers used data from the long-running FinnBrain Birth Cohort Study. They focused on a group of 55 Finnish men, selecting participants based on how much childhood adversity they reported using a standardized questionnaire called the Trauma and Distress Scale. The researchers then compared two groups: one made up of men with high scores—meaning more childhood maltreatment—and one with low scores.

The researchers analyzed sperm samples from these men to investigate two key molecular features: small non-coding RNAs and DNA methylation. Small non-coding RNAs, including microRNAs and tRNA-derived fragments, help regulate gene activity and are thought to play a role in early embryonic development. DNA methylation is a chemical tag that can silence or activate genes and is also considered an important regulator during development. The team used advanced sequencing techniques to map these features across the sperm cells, ensuring high-quality data while controlling for variables such as age, smoking, alcohol use, and mental health symptoms.

They found notable differences between the two groups. Specifically, 68 small RNAs—including 29 microRNAs and 21 tRNA fragments—were expressed at different levels in the sperm of men with high childhood trauma. One of the strongest findings involved a molecule called miR-34c-5p, which was consistently lower in men with higher adversity scores. This result matched earlier studies that also found reduced levels of this RNA in men who experienced childhood stress. Notably, miR-34c-5p is involved in brain development and is passed from sperm to the embryo during fertilization, potentially influencing how the brain forms.

“The biggest, and positive surprise was that we were able to replicate findings from a prior human study regarding one of the micro-RNA molecules. This is encouraging for future research efforts.”

In addition to small RNAs, the researchers also identified three regions of the genome that showed lower levels of DNA methylation in men who had experienced more childhood adversity. These regions were located near genes that are known to play important roles in the developing brain. One such gene, CRTC1, has been linked to mood disorders and memory. Another, GBX2, is involved in forming the neural plate and other early brain structures. The third gene, WFIKKN1, is primarily involved in muscle development, but its potential effects on offspring remain uncertain.

What makes these findings particularly compelling is that the epigenetic signatures remained significant even after adjusting for a range of lifestyle and health variables. This suggests that the patterns are not simply the result of poor health or lifestyle choices in adulthood, but may instead reflect long-term biological changes stemming from early life experiences.

“Different exposures like environmental toxins and stress exposure can affect the sperm epigenome. Our study found statistically robust associations between childhood maltreatment exposure and sperm epigenome, which implies that early life stress can have lasting impacts on gametes. While inheritance was not assessed in this study, our results provide basis for testing a very important question: can the epigenetic modifications cause heritable changes in humans?”

However, the study also has limitations. Although it includes the largest human sample to date for this kind of sperm analysis, the number of participants is still relatively small. The researchers relied on self-reported data to assess childhood maltreatment, which could be affected by memory or bias. They also examined sperm samples at a single time point, so it’s unclear how stable these epigenetic markers are over time.

Future research will be needed to follow children conceived by men with and without these epigenetic markers to see if differences emerge in development. The research team hopes to expand their work.

“Looking into to the future, we plan to continue with the data from FinnBrain Birth Cohort study to carry similar analyses in larger sample sizes and see if we find associations to offspring outcomes. I also have high hopes to be able to establish a new cohort study building on this research.”

The study, “Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm,” was authored by Jetro J. Tuulari, Matthieu Bourgery, Jo Iversen, Thomas Gade Koefoed, Annukka Ahonen, Ammar Ahmedani, Eeva-Leena Kataja, Linnea Karlsson, Romain Barrès, Hasse Karlsson, and Noora Kotaja.