Handling during pregnancy in the blue fox (Alopex lagopus): the influence on the fetal pituitary-adrenal axis

Previous studies revealed that handling is a stressor for farmed blue foxes. The present study was designed to examine the effects of a 1-min daily handling stress applied to pregnant blue fox vixens on the function of the fetal pituitary-adrenal system. Plasma concentrations of adrenocorticotropin hormone (ACTH), cortisol, and progesterone, adrenal content of cortisol and progesterone, in vitro adrenal production of these steroids and response to ACTH, and adrenal weights were measured in control (C; n = 73) and stressed (S; n = 58) fetuses. The ACTH levels were lower in stressed fetuses than in the controls (C: males, 128.6 +/- 6.1 pg/ml; females, 165.9 +/- 6.1 pg/ml; S: males, 122.3 +/- 5.4 pg/ml; females, 145.0 +/- 8.1 pg/ml; P < 0.05). In contrast, increased plasma cortisol concentrations in both sexes were demonstrated in stressed compared with control fetuses (C: males, 9.2 +/- 0.4 ng/ml; females, 9.2 +/- 0.4 ng/ml; S: males, 11.8 +/- 0.7 ng/ml; females, 13.2 +/- 0.7 ng/ml; P < 0.00001). The same difference was observed in plasma progesterone concentrations (C: males, 1.54 +/- 0.07 ng/ml; females, 1.49 +/- 0.10 ng/ml; S: males, 1.86 +/- 0.11 ng/ml; females, 1.74 +/- 0.10 ng/ml; P < 0.01). Prenatal stress did not change the baseline adrenal production of cortisol but prevented the cortisol response to ACTH in female fetuses and decreased the progesterone production in both sexes. Additionally, prenatally stressed fetuses of both sexes had significantly lower adrenal weights than controls (C: males, 9.4 +/- 0.3 mg; females, 9.5 +/- 0.4 mg; S: males, 8.1 +/- 0.3 mg; females, 8.2 +/- 0.4 mg; P < 0.001). These results indicate that prenatal handling stress induces a dysregulation of the pituitary-adrenal axis in the fetus and suggest that increased plasma glucocorticoids in the stressed dam can cross the placenta and influence the fetal hypothalamicpituitary-adrenal axis.