Maternal stress has been identified as a critical factor that influences the long-term health of offspring across generations. A recent study by King et al. published in Communications Biology profiled the effects of prenatal maternal stress on DNA methylation and gene expression in placenta and fetal cortex samples across four generations (F0–F3) of a well-characterized rat cohort. Exposure to prenatal maternal stress during a critical period for epigenetic programming (embryonic days 12–18) led to cumulative changes in the F2 and F3 generations, which were more pronounced than those observed in the F1 generation. Transgenerational programming primarily identified genes and biological pathways associated with neurological and psychiatric disorders, which were linked to maternal–fetal interactions mediated by the placenta. This study enhances our understanding of the molecular mechanisms that underlie developmental changes caused by prenatal maternal stress and suggests that the placenta is a potential source of predictive biomarkers for neurodevelopmental health.

Original reference: Commun. Biol. 8, 38 (2025)