Prenatal stress is associated with increased vulnerability to neurodevelopmental disorders, including autism and schizophrenia. This study examined the effects of stress during early, mid, and late gestation on offspring behavior and found that male offspring exposed to stress early in pregnancy showed maladaptive behavioral stress responses, anhedonia, and increased sensitivity to selective serotonin reuptake inhibitor (SSRI) treatment. Long-term changes in corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, as well as increased hypothalamic-pituitary-adrenal (HPA) axis responsivity, were observed in these mice, suggesting a role in elevated stress sensitivity. Epigenetic changes, including DNA methylation, were linked to altered gene expression, indicating that early prenatal stress can program the offspring's stress response. The study also found that stress early in pregnancy increased the expression of PPARα, IGFBP-1, HIF3α, and GLUT4 in male placentas but not in females, highlighting sex-specific placental responsiveness. These findings suggest that early prenatal stress may contribute to male neurodevelopmental disorders through impacts on placental function and fetal development. The results emphasize the importance of understanding sex-specific programming in pregnancy to develop targeted interventions for neurodevelopmental and mood disorders.Prenatal stress is associated with increased vulnerability to neurodevelopmental disorders, including autism and schizophrenia. This study examined the effects of stress during early, mid, and late gestation on offspring behavior and found that male offspring exposed to stress early in pregnancy showed maladaptive behavioral stress responses, anhedonia, and increased sensitivity to selective serotonin reuptake inhibitor (SSRI) treatment. Long-term changes in corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, as well as increased hypothalamic-pituitary-adrenal (HPA) axis responsivity, were observed in these mice, suggesting a role in elevated stress sensitivity. Epigenetic changes, including DNA methylation, were linked to altered gene expression, indicating that early prenatal stress can program the offspring's stress response. The study also found that stress early in pregnancy increased the expression of PPARα, IGFBP-1, HIF3α, and GLUT4 in male placentas but not in females, highlighting sex-specific placental responsiveness. These findings suggest that early prenatal stress may contribute to male neurodevelopmental disorders through impacts on placental function and fetal development. The results emphasize the importance of understanding sex-specific programming in pregnancy to develop targeted interventions for neurodevelopmental and mood disorders.