Introduction. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. Methods. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100？μg/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10–E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. Results. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. Conclusion. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols. 1. Introduction The concept of the fetal genome is no longer that of a static framework inherited from paternal and maternal sources but a malleable scaffold constantly adapting to stimuli. This is most evident in studies involving fetal programming due to the effects of nutritional variation and glucocorticoid exposure [1]. Here, we examined the resulting fetal molecular preconditioning due to antenatal steroid therapy using a protein-restriction mouse model. This model was first designed in a previous study [2] as a novel approach to evaluate postnatal adaptive responses due to varied prenatal nutritional conditions and the addition of stress or steroids. Molecular evidence revealed that prenatal programming secondary to maternal protein restriction rendered an inherent susceptibility to neural compromise in neonates and any further addition of antenatal steroids may be detrimental to these already injury-prone offspring. Thus, an examination of underlying molecular mechanisms in the fetus was warranted to elucidate the effects seen
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