Prenatal Stress May Pose Greater Emotional and Immune Risks for Female Children, Study Finds

Recent research led by experts from the Hebrew University of Jerusalem reveals that stress experienced by mothers during pregnancy can have profound molecular effects on their offspring, particularly impacting female newborns. The study, published in Molecular Psychiatry, emphasizes that prenatal perceived stress (PPS)—the mother’s own psychological stress—can reprogram critical molecular pathways in the fetus, notably those related to the cholinergic system responsible for managing stress responses and inflammation.

Researchers analyzed umbilical cord blood from over 120 mother-infant pairs and focused on tiny RNA molecules called tRNA fragments (tRFs), which influence gene activity similarly to microRNAs. The findings were striking: maternal stress induced significant alterations across entire families of tRFs, especially those originating from mitochondrial DNA. These changes were highly sex-dependent, with female infants displaying the most substantial shifts. Notably, there was a near-total reduction in certain mitochondrial-derived tRFs, known as 'CholinotRFs,' which target genes involved in acetylcholine production—a neurotransmitter vital for brain performance and immune regulation.

Further analysis showed that newborns of stressed mothers, particularly males, had elevated levels of acetylcholinesterase (AChE), an enzyme that degrades acetylcholine, hinting at a disrupted stress response system from birth. This molecular imprinting might explain heightened vulnerability to neurodevelopmental and psychiatric disorders later in life.

Using advanced machine learning, the team demonstrated that female newborns’ TRF profiles could accurately identify exposure to maternal stress, with an impressive classification success rate of 95%. This suggests potential diagnostic tools for early detection of prenatal stress effects, enabling timely intervention.

Prof. Hermona Soreq and Shani Vaknine Treidel explained that these findings underscore the importance of mental health awareness during pregnancy, as maternal psychological well-being can leave lasting biological marks on the offspring. The study was part of the international FELICITy project, in collaboration with institutions like the Technical University of Munich and the University of Washington.

This research highlights how prenatal environmental factors shape future health, emphasizing the need for supportive mental health strategies for pregnant women to ensure better emotional and immune outcomes for their children.