Summary: A new study reveals that stress during pregnancy can molecularly reprogram newborns’ stress response systems, with significant differences between boys and girls. Researchers found that maternal stress altered entire families of tRNA fragments in umbilical cord blood, particularly those regulating acetylcholine, a key neurotransmitter.
These changes were most dramatic in female newborns and were linked to an imbalance in stress regulation mechanisms. The findings highlight the importance of addressing maternal mental health for the lifelong wellbeing of children.
Key Facts:
- Sex-Specific Effects: Maternal stress caused more dramatic molecular changes in female newborns.
- Cholinergic System Disruption: Stress reprogrammed tRNA fragments regulating acetylcholine, affecting brain and immune function.
- Early Detection Potential: Machine learning could classify exposed newborns with 95% accuracy based on molecular profiles.
Source: Hebrew University of Jerusalem
A new study led by Prof. Hermona Soreq and Shani Vaknine Treidel from the Edmond and Lily Safra Center of Brain Science (ELSC) at Hebrew University, 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.
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.
About this stress, pregnancy, and genetics research news
Author: Hermona Soreq
Source: Hebrew University of Jerusalem
Contact: Hermona Soreq – Hebrew University of Jerusalem
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns” by Hermona Soreq et al. Molecular Psychiatry
Abstract
Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns
Maternal perceived prenatal stress (PPS) is a known risk factor for diverse developmental impairments in newborns, but the underlying molecular processes are incompletely understood.
Here, we report that maternal PPS altered the birth profiles of blood transfer RNA fragments (tRFs), 16–50 nt long non-random cleavage products of tRNAs, in a sex-dependent manner.
Importantly, comparing stressed versus control maternal and umbilical cord blood serum presented alterations that were not limited to individual tRFs, but rather reflected selective changes in particular tRF families grouped by their mitochondrial or nuclear genome origin, parental tRNA coded amino acid, and cleavage type.
Specifically, tRF families that show stress- and sex-specific effects, revealed shared length and expression patterns which were strongest in the female newborns.
Several of these tRFs carry complementary motifs to particular cholinergic mRNAs, suggesting possible translational regulation similar to microRNAs.
Compatible with the cholinergic regulation of stress reactions, those “CholinotRFs” achieved an AUC of 95% when classifying female newborns according to maternal PPS.
Moreover, we found altered catalytic activity of serum acetylcholinesterase, which was particularly elevated in male newborns, marking a second sex-specific effect.
Our findings demonstrate an association of tRF families’ patterns with newborns’ sex-specific stress response to PPS and may lead to better diagnosis and therapeutic tools for these and other stressors.
