this study for the first time demonstrated the presence of three different GRα-BNC-subtypes in sheep placenta. The number of GRα BNCs was regulated by early DEX treatment and this effect was long lasting and sex-, subtype-, placentome-subtype- and level-dependent. Early in pregnancy, DEX may reduce the function of BNCs via increased proportion of "inactive" BNC compared to controls. Apoptosis may play an important role in the conversion among the three BNC-subtypes. This is supported by co-localisation studies with caspase-3, oPL and GRα. Late in pregnancy, early DEX treatment resulted in an increased mean percentage of "active" BNC and decreased the mean percentage of "inactive/intermediate" BNC compared to controls, suggesting that early DEX treatment possibly reduces the sensitivity of GRα in BNCs to the natural rise of fetal cortisol levels near term. While in female fetuses a constant placental GC sensitivity is maintained, possibly in terms of a preferential survival strategy for ensuring reproductive capacity and species conservation, it seems that in male fetuses, due to increased GC exposure, the placenta becomes at least temporarily GC-resistant.