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 structure and function of the adrenal glands of fetal and neonatal offspring have been investigated by combined stereological and ultrastructural methods, as well as by metaphase index determination. Pregnant rats were injected subcutaneously with Dx (0.3 mg/kg body weight/day) during 5 days, starting from day 16 of gestation. The dams and their fetuses were killed 24 hr after the last injection. The neonatal 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 (ZR) 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 activity of adrenocortical cells was estimated following the application of Vincristine sulphate. Dx treatment of pregnant rats induced a marked decrease of fetal adrenal gland volume and the volumes of zona glomerulosa + capsula (ZG + C) and IZ as the consequence of atrophic changes in the gland and reduction of the average volume and total number of adrenocortical cells. Similar morphometric changes were found in 3- and 14-day-old pups. However, in 3-day-old animals the number of cortical cells in the ZG was increased, whereas on the 14th postnatal day cortical cell number remained decreased only in the ZF. The multinuclear giant cells, numerous lymphocytes, and the resorption zones, present in the adrenal cortex of fetuses and 3-day-old pups of both experimental and control dams, were not seen in 14-day-old offspring. These results demonstrate that prolonged treatment of pregnant rats with Dx in the period when intensive differentiation of the fetal hypothalamo-hypophyseal system takes place inhibits proliferative activity of adrenocortical cells and evokes considerable atrophic changes in the adrenal glands of offspring from 20 days gestation to 14 days after birth. The histological appearance of the adrenal cortex and the ultrastructure of adrenocortical cells suggest that cortical cell function was inhibited.
Hristić
M
M
Faculty of Pharmacy, Department of Physiology, University of Belgrade, Yugoslavia.
Kalafatić
D
D
Plećas
B
B
Manojlović
M
M
D000311:Adrenal Glands / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D008677:Metaphase / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D003907:Dexamethasone