THE INFLUENCE OF PROLONGED DEXAMETHASONE TREATMENT OF PREGNANT RATS ON THE PERINATAL-DEVELOPMENT OF THE ADRENAL-GLAND OF THEIR OFFSPRING

The effects of prolonged dexamethasone (Dx) administration to pregnant rats on the struture and function of the adrenal glands of fetal and neonatal offspring have been investigated by combined stereological an d ultrastructural methods, as well as by metaphase index determination . Pregnant rats were injected subcutaneoisly with Dr (0.3 mg/kg body w eight/day) during 5 days, starting from day 16 of gestation. The dams and their fetuses were killed 24 hr after the last injection. The neon atal offspring were killed in the same way on the 3rd and 14th day of life. Because in fetal and 3-day-old neonatal rats zona reticularis (Z R) was poorly defined and could not be clearly seen as a separate zone , zona fasciculata (ZF) and ZR were analyzed as one, inner zone (IZ). In 14-day-old rats ZF and ZR were analyzed separately. Proliferative a ctivity of adrenocortical cells was estimated following the applicatio n of Vincristine sulphate.Dx treatment of pregnant rats induced a mark ed decrease of fetal adrenal gland volume and the volumes of zona glom erulosa + capsula (ZG + C) and IZ as the consequence of atrophic chang es in the gland and reduction of the average volume and total number o f adrenocortical cells. Similar morphometric changes were found in 3- and 14-day-old pups. However, in 3-day-old animals the number of corti cal cells in the ZG was increased, whereas on the 14th postnatal day c ortical cell number remained decreased only in the ZF. The multinuclea r giant cells, numerous lymphocytes, and the resorption zones, present in the adrenal cortex of fetuses and S-day-old pups of both experimen tal and control dams, were not seen in 14-day-cold offspring. These re sults demonstrate that prolonged treatment of pregnant rats with Dr in the period when intensive differentiation of the fetal hypothalamo-hy pophyseal system takes place inhibits proliferative activity of adreno cortical cells and evokes considerable atrophic changes in the adrenal glands of offspring from 20 days gestation to 14 days after birth. Th e histological appearance of the adrenal cortex and the ultrastructure of adrenocortical cells suggest that cortical cell function was inhib ited, too. (C) 1997 Wiley-Liss, Inc.