Prenatal stress effects on offspring brain and behavior: Mediators, alterations and dysregulated epigenetic mechanisms

Prenatal environment significantly influences mammalian fetal development and adverse in utero conditions have life-long consequences for the offspring health. Research has revealed that a wide variety of prenatal stress factors lead to increased risk of vulnerability to neuropsychiatric disorders in the individuals. Multiple mediators are involved in stress transfer from mother to the developing fetus, with stress hormone cortisol being a chief player. Further, the developmental programming effects of prenatal stress have been observed in the form of alterations in the offspring brain at different levels. This review covers stress transfer mediators such as cortisol, serotonin, maternal cytokines, reactive oxygen species (ROS) and the maternal microbiota, and their role in fetal programming. Prenatal stress leads to alterations in the offspring brain at multiple levels, from molecular and cellular to structural. These alterations eventually result in lasting phenotypic alterations such as in the offspring behavior and cognition. Different brain alterations induced by prenatal stress such as in neural pruning processes, neural circuit formation, brain structural connectivity and epigenetic systems regulating neural gene expression are under focus in the second part of the review. The latter constitutes a key molecular mechanism involved in prenatal stress effects and has been discussed in more detail.