Fetal corticosterone exposure leads to enhanced visceral hypersensitivity and is associated with down-regulation of placental 11-beta-steriod dehydrogenase 2

We previously show that chronic prenatal stress (CPS) produces enhanced visceral hypersensitivity (VHS) in female offspring following exposure to chronic adult stress (CAS) that is of greater magnitude and duration in adult female than in male offspring. We tested the hypothesis that CPS elevates fetal plasma corticosterone (CS) to produce enhanced VHS in female offspring following CAS and that down-regulation of placental 11-beta-steriod dehydrogenase 2 (11ß-HSD-2) during CPS contributes to elevated fetal CS. Significant increases in plasma CS levels were found in both male and female fetuses from CPS dams on E14, 16, 18 and 20 that were significantly higher in females than males. Adult female offspring of dams treated with either corticosterone or the 11ß-HSD-2 inhibitor carbenoxolone from embryonic day (E) 11 to E21 developed significantly greater VHS compared to offspring of vehicle treated, unstressed dams. We found significant decreases in 11-b-HSD2 expression in placentas associated with both male and female fetuses from CPS dams that was significantly greater in CPS females. CPS significantly elevated norepinephrine (NE) levels in CPS dams. Treatment of CPS dams with both phentolamine and propranolol before each stressor significantly attenuated the decrease in 11-b-HSD2 expression in placentas associated with female fetuses in CPS dams compared to vehicle treatment, p=0.022, and significantly reduced VHS in adult female offspring following CAS, but not males. These findings support a role for elevated fetal CS levels caused by prenatal stress in the development of enhanced VHS in adult females following chronic adult stress.

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