Abstract

Prenatal stress (PS) has been mainly investigated in animal models. It could trigger permanent neurobiological changes in the offpring through fetal programming, displayed as behavioral, cognitive, anxious, affective and psychotic disorders during infancy and adulthood. Main effects of PS have been related to the functioning of hypothalamic-pituitary-adrenal axis (HPA), serotonergic, glutamatergic and GABAergic systems, cortical (prefrontal, temporal and insular cortex) and subcortical structures (amygdala, hippocampus), cerebellum and placenta. Glucocorticoids are the most recognized transmission factors of maternal-fetal stress, with distinctive effects according to the moment of action, developmental stage and fetal gender. Alteration pattern of the HPA axis by PS would be similar to the one observed in some mental disorders. Other neuromodulators involved in the neurotoxicity of PS are nitric oxide and brain derived neurotrophic factor, associated to synaptic potentiation and depression. Also, serotonergic system has an important relationship with HPA axis, verifyinga decreased number of serotonin transporters and an impaired placental synthesis of the neurotransmitter, essential for fetal neurodevelopment. Other epigenenomic mechanisms would be the modulation of synaptic plasticity by neurotrophins, adhesion and membrane molecules. Treatment with selective serotonin reuptake inhibitors has shown controversial outcomes. PS would affect fetal programming causing significant and permanent neurobiological alterations with clinical manifestations. This complex phenomenon must be further investigated, especially in human models.