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The present study show that maternal adrenalectomy affect the developmental model of the dopaminergic system in the hypothalamus and hippocampus, with sexual dimorphism observed in both areas. No changes were observed in the developmental dopamine (DA) model of the cortex and striatum through dopamine levels were increased in striatum.

Maternal adrenal steroid hormones have been proven to be crucial for lung and adrenal prenatal maturation. These hormones mediate the effects of prenatal stress crossing the placenta and influencing the development of the hypothalamus-pituitary-adrenal axis of fetuses. In the present study, we have compared the prenatal development of fetuses from adrenalectomized mothers (ADX group) and from sham-operated mothers. We have used immunohistochemistry for calcium binding-protein Calbindin-D28k, astroglial proteins vimentin and glial fibrillary acidic protein (GFAP), and the ultrastructural differentiation of the cerebral cortex and hippocampus to measure putative differences. The ontogeny of the Calbindin-D28k immunoreactivity was delayed, as transient Calbindin-positive neuronal populations in the ADX group disappeared later during development as compared to that of control animals both in cerebral cortex and hippocampus; cell counts revealed that ADX animals had a significantly higher number of Calbindin-positive cells than controls in the cerebral cortex, while that number was lower in ADX fetuses' hippocampus. Cerebral cortex of ADX animals also had a scattered distribution of stained cells compared with controls, while the hippocampi of the ADX animals had an impaired migration of marginal zone interneurons. No GFAP immunoreactivity was found in the studied prenatal stages. Instead, vimentin-immunoreactivity appeared more profusely distributed throughout the cerebral cortex, in the ADX group than in control animals. At the ultrastructural level, no remarkable differences were found before E20, when a higher undifferentiation in the ADX group, in both cerebral cortex and hippocampus, was evident. The results show for the first time the vulnerability of the prenatal rat brain to maternal adrenalectomy and the necessity of maternal glucocorticoids for encephalic development.

In order to determine the incidence of maternal glucocorticoids on morphological parameters in fetal development, we performed optic and electron microscopic analysis of the cerebral cortex of fetuses of 16 and 20 days of gestation, from control (C) and pregnant rats bilaterally adrenalectomized on day 1 of gestation (ADX). We also studied fetuses 20 days old from pregnant rats betamethasone-injected on days 15, 16 and 17 (BET), and adrenalectomized on day 1 and betamethasone-injected on days 15, 16 and 17 (ADX+BET). Absence of maternal glucocorticoids during gestation caused, in fetuses 16 and 20 days old, a marked increase of cellular density, laxity of tissue and lower cellular maturation in comparison with the control group. Beta-methasone injected into sham-operated animals (BET) caused a slight advance in relation to controls in developmental parameters such as cellular density, maturation and synapse formation. Betamethasone injection into adrenalectomized animals prevented the lower degree of maturation characteristic of the adrenalectomized group, although an increase of cellular density could be detected. The cerebral cortex from fetuses of 16 days of gestation from adrenalectomized mothers also showed an increase of cellular density as compared with the control group. These results show that glucocorticoids participate in prenatal rat brain in control mechanisms of cellular division and maturation.

Optic and electron microscopic analysis were performed on the hippocampus of fetuses of 20 days gestation, from pregnant rats bilaterally adrenalectomized on day 1 of gestation (ADX) and control (C), in an attempt to determine the incidence of maternal glucocorticoids on morphological parameters in fetal development. In addition, we studied 20 day old fetuses from pregnant rats betamethasone-injected on days 15, 16 and 17 (BET), and adrenalectomized on day 1 and betamethasone-injected on days 15, 16 and 17 (ADX + BET). The adrenalectomy led to a decreased total cell number and a marked depletion of the dentate gyrus of the hippocampus, and also to widespread indifferentiation, both in the pyramidal cell layer of the Ammon's horn and the dentate gyrus, as well as a decreased cell number in CA3 stratum pyramidale. No differences in cell number were found in CA1. So, the ADX effect is in relation to the neurogenic gradient. The main effect of the exogenous glucocorticoid treatment was increased maturation in relation to the control group. Betamethasone injection in adrenalectomized animals prevented the lower degree of maturation of the adrenalectomized group but not the impaired cell number. These results show that glucocorticoids participate in prenatal hippocampus in control mechanisms of cellular division and in maturation.