by Hebrew University of Jerusalem

Study layout and participant characteristics. Credit: Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03011-2

A new study led by Prof. Hermona Soreq and Shani Vaknine Treidel from the Edmond and Lily Safra Center of Brain Science, uncovers how stress experienced during pregnancy can affect newborns at the molecular level—with significant differences between male and female babies.

The study, published in Molecular Psychiatry, focused on perceived prenatal stress (PPS)—the mother's own sense of psychological stress during pregnancy—and discovered that it can reprogram key molecular pathways in the baby's body, especially those linked to the cholinergic system, which governs stress response and inflammation.

"We found that even before babies take their first breath, the stress their mothers experience can shape how their bodies manage stress themselves, " said Prof. Soreq.

The team analyzed umbilical cord blood from babies born to mothers who reported high stress levels during the third trimester. They focused on small RNA molecules called tRNA fragments (tRFs), which regulate gene expression much like microRNAs. What they found was remarkable: the stress didn't just alter individual tRFs—it affected entire families of tRFs, particularly those with origins in mitochondrial DNA.

These changes were sex-specific, with female newborns showing the most dramatic shifts, including a near-complete decline in specific mitochondrial tRFs. Many of these tRFs, termed "CholinotRFs, " target genes that govern acetylcholine, a neurotransmitter essential for both brain function and immune regulation.

tRF families differ significantly between stressed and control groups, with some inverse effects between mothers and newborns. Credit: Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03011-2

The study also measured levels of acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine. Newborns of stressed mothers—especially boys—had significantly higher levels of AChE, suggesting an imbalance in their stress-response system right from birth.

These molecular changes could help explain why children exposed to high maternal stress during pregnancy may be more vulnerable to neurodevelopmental and psychiatric conditions later in life.

By using machine learning techniques, the researchers were able to accurately classify female newborns as exposed or unexposed to maternal stress based on their CholinotRF profiles, achieving a classification success rate (AUC) of 95%. This opens the door to new diagnostic tools for detecting prenatal stress effects and possibly even early interventions.

"This study provides a powerful glimpse into how the maternal environment can leave a lasting biological imprint on the next generation, " said Vaknine Treidel. "It also underscores the importance of recognizing and supporting mental health during pregnancy—not just for the mother, but for the lifelong health of the child."

This study was conducted as part of the international FELICITy project, in collaboration with the Technical University of Munich and the University of Washington, among others. Blood samples were collected from over 120 mother-infant pairs and analyzed at the Hebrew University's Center for Genomic Technologies.

More information: Shani Vaknine Treidel et al, Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns, Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03011-2  Journal information: Molecular Psychiatry