CONICET | Buscador de Institutos y Recursos Humanos

Epidemiological studies in humans and experiments in rodents suggest that adverse environmental conditions during embryonic development program physiology later in life. Stress exposure during pregnancy induces long-lasting detrimental consequences in the offspring that seem to be related to an altered function-interaction of the circadian and stress systems. The programming effects of prenatal stress are usually studied in animals subjected to various forms of stress, either at fixed or at unpredictable times. Such multifaceted interventions complicate the mechanistic examination of the underlying processes. To simplify this, we developed a "chrono-stress" paradigm. The stressor was a single and timed injection of corticosterone either in the morning (CORTm, in anti-phase to the maternal circadian glucocorticoid (GC) rhythm) or in the evening (CORTe in phase with maternal GCs), every day during the second half of gestation. The offspring were tested for circadian and stress-related responses as young adults. We found that the time of the day when the mother is exposed to CORT, is an important programming factor, determining the severity of the adult offspring's phenotype. The offspring of CORTm mothers showed elevated anxiety levels (less open arm entries in the elevated plus maze), impaired stress resistance (longer immobility periods in the forced swim test), high basal GCs production and impaired response to acute stress compared to CORTe (and non-stressed control) offspring. This phenotype was accompanied by a differential expression of glucocorticoid receptor (GR) and GR-target genes, indicating an altered GR sensitivity of at central and peripheral levels. Our results indicate the presence of a circadian gating mechanism determining the programming effects of prenatal stress exposure.