Maternal glucocorticoid secretion mediates long-term effects of prenatal stress

Abstract

There is growing evidence that stressors occurring during pregnancy can impair biological and behavioral adaptation to stress in the adult offspring. Mechanisms by which stress in the pregnant rat can influence development of the offspring are still unknown. In the present study, we investigated the involvement of maternal corticosterone secretion during pregnancy on the hypothalamo-pituitary-adrenal axis activity of adult offspring. We investigated stress-induced corticosterone secretion and hippocampal type I and type II corticosteroid receptors in male adult rats submitted to prenatal stress born to either mothers with intact corticosterone secretion or mothers in which stress-induced corticosterone secretion was blocked by adrenalectomy with substitutive corticosterone therapy. Repeated restraint during the last week of pregnancy was used as prenatal stressor. Furthermore, the specific role of an injection of corticosterone before the restraint stress on adrenalectomized mothers with substitutive corticosterone treatment was also studied. We report here that blockade of the mother's stress-induced glucocorticoid secretion suppresses the prolonged stress-induced corticosteroid response and the decrease in type I hippocampal corticosteroid receptors usually observed in prenatally stressed adults. Conversely, corticosterone administered during stress, to mothers in which corticosterone secretion is blocked, reinstates the effects of prenatal stress. These results suggest for the first time that stress-induced increases in maternal glucocorticoids may be a mechanism by which prenatal stress impairs the development of the adult offspring's glucocorticoid response.

Fig. 1.

Plasma corticosterone secretion after restraint stress in control and prenatally stressed offspring of mothers with intact (14–20 animals/group) or blocked (7–10 animals/group) stress-induced corticosterone secretion. The experimental groups did not differ in corticosterone secretion in basal conditions (left panel) or 30 min after stress (middle panel). At 120 min after stress (right panel), prenatally stressed animals, the mothers of which were in the intact group, had higher corticosterone levels than controls. Prenatally stressed rats whose mothers’ corticosterone secretion was blocked did not differ from controls. ***p < 0.001. Error bars represent SEM.

Fig. 2.

Hippocampal corticosteroid receptors in control and prenatally stressed offspring of mothers with intact (14–20 animals/group) or blocked (7–10 animals/group) stress-induced corticosterone secretion. Type I corticosteroid receptors were lower in prenatally stressed rats from mothers with intact corticosterone secretion, whereas prenatal stress had no effect on this measure when maternal corticosterone secretion was blocked (left panel). No significant effects were found on theB_max of type II receptors (right panel) or in the affinity of either receptor type. Mean affinities were (in nm): type I = 1.66 ± 0.17; type II = 1.14 ± 0.21. ***p < 0.001. Error bars represent SEM.

Fig. 3.

Plasma corticosterone secretion after restraint stress in prenatally stressed rats, the mothers of which had either low (5–10 animals/group) or high (10–14 animals/group) corticosterone levels when submitted to stress during pregnancy. There were no significant differences in corticosterone secretion in basal conditions (left panel) or 30 min after stress (middle panel), whereas prenatally stressed rats from mothers having high corticosterone levels had a prolonged stress-induced corticosterone secretion (right panel). ***p < 0.001. Error bars represent SEM.

Fig. 4.

Hippocampal corticosteroid receptors in rats, the mothers of which had either low (5–10 animals/group) or high (10–14 animals/group) corticosterone levels when submitted to stress during pregnancy. Type I corticosteroid receptors were lower in animals from mothers having high corticosterone levels (left panel). No differences were found in the B_max of type II receptors (right panel) or in the affinities of either receptor type. Mean affinities were (in nm): type I = 1.71 ± 0.15; type II = 1.56 ± 0.30. ***p < 0.001. Error bars represent SEM.