A recent study has uncovered how stress experienced by mothers during pregnancy can leave a molecular imprint on their babies, influencing their health long before birth. The research highlights how prenatal stress alters the expression of small RNA molecules in newborn blood, particularly in girls, and affects critical enzymes in the brain’s stress-regulation system. These findings may offer new insights into why some children are more susceptible to developmental and psychiatric challenges, while also paving the way for early diagnosis and potential interventions for stress-related health risks.
Led by Prof. Hermona Soreq and Shani Vaknine Treidel from the Edmond and Lily Safra Center of Brain Science (ELSC) at Hebrew University, the study sheds light on how perceived prenatal stress (PPS)—the psychological stress experienced by mothers during pregnancy—can impact molecular pathways in babies, with significant differences between male and female infants.
The study, published in Molecular Psychiatry, focused on how PPS reprograms the cholinergic system, which plays a central role in the 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,” said Prof. Soreq.
To investigate these changes, the research team analyzed umbilical cord blood from babies born to mothers who reported high levels of stress during the third trimester of pregnancy. The focus was on small RNA molecules called tRNA fragments (tRFs), which regulate gene expression in a manner similar to microRNAs. The results were striking: prenatal stress did not merely alter individual tRFs, but affected entire families of tRFs, particularly those originating from mitochondrial DNA.
The changes were found to be sex-specific, with female newborns showing the most significant alterations. Specifically, there was a near-complete decline in certain mitochondrial tRFs in girls. Many of these tRFs, known as “CholinotRFs,” target genes responsible for acetylcholine production, a neurotransmitter critical for both brain function and immune regulation.
Additionally, the study measured levels of acetylcholinesterase (AChE), an enzyme responsible for breaking down acetylcholine. Newborns, particularly boys, from stressed mothers had significantly higher levels of AChE, suggesting an imbalance in their stress-response system from birth.
These molecular changes may help explain why children exposed to high maternal stress during pregnancy are more vulnerable to neurodevelopmental and psychiatric disorders later in life.
The researchers used machine learning techniques to analyze the CholinotRF profiles and successfully identified whether female newborns had been exposed to prenatal stress with a high degree of accuracy—95% classification success. This breakthrough opens the possibility of developing diagnostic tools to detect the effects of prenatal stress and potentially intervene early to mitigate associated health risks.
“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 emphasizes the importance of supporting mental health during pregnancy, not only for the well-being of the mother but also for the lifelong health of the child.”
The study was part of the international FELICITy project, in collaboration with the Technical University of Munich and the University of Washington, among others. Blood samples from over 120 mother-infant pairs were analyzed at Hebrew University’s Center for Genomic Technologies.
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