25 Apr HebrewU: Sex-Specific Effects of Maternal Mental Stress Produces Detectable Molecular Signature in Newborn

MedicalResearch.com Interview with:

Prof. Hermona Soreq

Prof. Hermona Soreq
Professor of Molecular Neuroscience
The Edmond and Lily Safra Center for Brain Sciences
Department of Biological Chemistry
The Alexander Silberman Institute of Life Sciences
The Hebrew University of Jerusalem
The Edmond J. Safra Campus, Givat Ram Jerusalem Israel and

Shani Vaknine

Shani Vaknine, Ph.D. candidate
Brain and Behavioral Sciences
The Hebrew University

MedicalResearch.com: What is the background for this study?

Response: We’ve long known that maternal stress during pregnancy can affect her baby’s development, but the molecular mechanisms behind this remained unclear. In our study, we explored how psychosocial stress experienced by the mother in late pregnancy influences tiny molecular fragments in the newborn’s blood. These fragments, called transfer RNA fragments or tRFs, were considered for many years to be disposable, but have recently been shown to have important biological functions.

MedicalResearch.com: What are the main findings?

Response:  We discovered that the levels and types of these fragments change depending on the baby’s sex and the mother’s stress. Further, we’ve shown that tRFs may work as “families”, divided according to their genome origin (Mitochondrial or Nuclear), cleavage type (out of five subtypes), and coded amino acid, that showed expression and length patterns that were context-specific. While female newborns showed larger tRF effects, we also observed altered activity of an enzyme called acetylcholinesterase (ACHE), a key player in the body’s stress response system, that was stronger in the male newborns. The opposite nature of these sex-specific effects aligns with the higher vulnerability of male newborns phenomenon and may suggest that the stronger female tRF response acts as a protective mechanism. Notably, the AChE protein’s activity terminates the process whereby acetylcholine signaling affects stress responses. Remarkably, a group of those tRFs that were predicted to target genes in the ACHE cholinergic pathway were able to classify female, but not male, newborns according to whether their mothers experienced stress with 95% accuracy.

MedicalResearch.com: What should readers take away from your report?

Response: Our findings show that the effects of the mental stress the mother experiences during pregnancy produce a molecular signature of the newborn, that is sex-specific and can be detected as early as birth takes place. These differences are visible in both cholinesterase enzyme activities and in tRF levels found in the umbilical cord blood, with male newborns showing larger enzyme activities and female newborns showing larger tRF effects. It suggests that stress leaves a biological fingerprint that could help us identify at-risk infants early and provide a window to intervene as soon as possible.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: As the tRF field is still in its relative beginning, future research should explore the group function of these fragments, and dig deeper into their specific biological functions. Moreover, larger and longer studies are needed to validate our results and test whether these biomarkers could predict long-term developmental outcomes. Investigating how these markers interact within the body stress-reaction may open doors to enable better diagnosis or even targeted therapies.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: Our study adds to a growing understanding of how early life exposures shape future health. We hope it will inspire more attention to maternal well-being during pregnancy, not only for the sake of protecting the mother’s health but for improving her child’s development. This work was performed as part of the FELICITy project, collaborating between institutions in Israel, Germany, and Argentina. We thank the participating families for their huge contribution to this study. We have no conflicts of interest to declare.

Citation: Vaknine Treidel, S., Lobmaier, S.M., Sharma, R. et al. Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03011-2

https://www.nature.com/articles/s41380-025-03011-2

More information:

• Prenatal stress can program a child’s brain for later health issues
  https://www.heart.org/en/news/2021/05/06/prenatal-stress-can-program-a-childs-brain-for-later-health-issues
• Laplante, D. P., et al. (2020). The Effects of Maternal Stress and Illness During Pregnancy on Infant Temperament: Project Ice Storm. Pediatric Research, 77(1), 107–113. Retrieved April 25, 2025, from https://www.nature.com/articles/pr2015203

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Last Updated on April 26, 2025 by Marie Benz MD FAAD