April 25, 2025 – Stress experienced by mothers during pregnancy leaves a prenatal molecular imprint on their babies, according to a new study by Hebrew University of Jerusalem researchers.
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.
“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. Hermona Soreq from the Edmond and Lily Safra Center of Brain Science (ELSC) at Hebrew University.
The research shows that prenatal stress alters the expression of tiny RNA molecules in newborn blood, particularly in female children, and affects key enzymes in the brain’s cholinergic system, which governs stress response and inflammation. These changes may help explain why some children are more vulnerable to developmental or psychiatric challenges. The study opens new possibilities for early diagnosis and interventions targeting stress-related health risks.
In the study, 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. 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.
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 ELSC’s 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.
The research paper titled “Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns” is now available in Molecular Psychiatry and can be accessed here.
Researchers:
Shani Vaknine Treidel1,2, Silvia M. Lobmaier3, Ritika Sharma3,4, Nimrod Madrer1, Serafima Dubnov1, Dana Shulman1, Pnina Greenberg1, Estelle R. Bennett1, David S. Greenberg1, Adi Turjeman5, Camilla Zelgert3, Peter Zimmermann3, Martin G. Frasch6, Liran Carmel2, Marta C. Antonelli3,7 and Hermona Soreq1
Institutions:
1) Department of Biological Chemistry and the Edmond and Lily Safra Center of Brain Science, the Hebrew University of Jerusalem, Jerusalem, Israel
2) Department of Genetics, the Hebrew University of Jerusalem, Jerusalem, Israel
3) Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany
4) Helmholtz Centre Munich, German Research Center for Health and Environment (GmbH), Munich, Germany
5) Genomic Center, the Hebrew University of Jerusalem, Jerusalem, Israel
6) Department of Obstetrics and Gynecology and Institute on Human Development and Disability (IHDD), University of Washington, Seattle, WA, USA
7) Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis”, Facultad De Medicina, UBA, Buenos Aires, Argentina.
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