Suppression of adernal cortical growth and differentiation in fetal rats exposed to dexamethasone

Abstract

The effects of maternal dexamethasone (DEXA) administration during the last days of gestation on fetal adrenal growth and differentiation were studied. Timed pregnant rats were divided into three groups: (a) 21d DEXA-3 received DEXA in drinking water (5 pg/ml) from days 18 to 21 of gestation; (b) 21d DEXAB received the same dosage of DEXA from days 15 to 21 of gestation; and (c) 21d control received tap water throughout gestation. On gestation day 21, pregnant rats were decapitated and bled into heparinized tubes; their fetuses were excised, weighed, decapitated, and bled. Fetal adrenals were prepared for electron microscopy or weighed and frozen until assayed for corticosterone. Control adrenals were also collected on day 15 of gestation and processed for electron microscopy only. Fetal adrenals were fixed in 2.5% glutaraldehyde in 0.5 M cacodylate buffer, postfixed in 2% osmium tetroxide (OsO$, dehydrated, and embedded in Epon 812. Twenty-one day (21d) fetal adrenal weights were 44% and 68% lower than control values for DEXA-3 and -6, respectively. Fetal adrenal corticosterone levels were decreased by 70% and 89% for the respective groups. These observations correlated with ultrastructural findings of decreased mitochondria1 number and size, altered orientation of the inner mitochondrial membrane, decreased lipid, and dilation of smooth endoplasmic reticulum (SER) in cortical fascicular cells of DEXA-exposed fetuses. Ultrastructural changes in the 21d DEXA fetal adrenals resembled 15d day control fetal adrenals. The results suggest suppressed adrenocortical differentiation probably due to DEXA inhibition of the steroidogenic influence of the fetal pituitary on the developing adrenal gland in DEXA-exposed fetuses.