Prenatal stress leads to deficits in brain development, mood related behaviors and gut microbiota in offspring

Abstract Early exposure to stressful and adverse life events at fetal and neonatal stages is one of crucial risk factors for mood disorders such as anxiety and depressive disorder in adulthood. Intergenerational effects of prenatal stress on offspring are still not fully understood. We here uncover a significant negative impact of prenatal stress on brain development in embryos and newborns, and on mood-related behaviors and gut microbiota in adult offspring. Prenatal stress leads to reduced numbers in neural progenitors and newborn neurons, and altered gene expression profiles in the mouse embryonic cerebral cortex. Adult mouse offspring exposed to prenatal stress displays altered gene expression in the cortex and elevated responses in anxiety- and depression-like behaviors. Interestingly, prenatal stress has an enduring effect on gut microbiota, as specific microbial community structure is altered in adult F1 offspring treated with prenatal stress, compared to that of the control. Our results highlight the essential impact of prenatal stress on cortical neurogenesis, gene expression patterns, mood-related behaviors, and even gut microbiota in the next generation.