Impact of Fetal Glucocorticoid Exposure on Gene Expression Profiles in the Adult Adrenal Gland

Abstract

An adverse in-utero environment increases the risk of development of adult diseases such as hypertension, diabetes and the metabolic syndrome. Although elevated circulating fetal levels of glucocorticoids are critically involved in programming events of adult diseases, the genetic basis is not completely understood. The aim of this study was to examine the impact of elevated fetal glucocorticoid levels on changes in gene expression in the adult adrenal gland via a genome-wide approach. The adrenal gland was selected for analysis since it secretes hormones that can directly influence cardiovascular, endocrine and metabolic functions. Total mRNA from adrenal glands was isolated from 5 wk old male CD1 mice exposed prenatally (GD14-21) via maternal injections of the synthetic glucocorticoid dexamethasone (DEX; 100 ug/kg/day i.p.) or saline (control). To probe changes in neuroendocrine transcriptome induced in fetal programming, total mRNA was hybridized to Affymetrix GeneChip Mouse Genome 430v2.0 Arrays (~39K genes). Data was analyzed using a model-based expression algorithm (dCHIP) and filtered (>1.5 fold change in gene expression; statistical significance, p<0.05). Results indicate that only 0.7% of genes (290 genes) were differentially expressed in adrenal glands of mice prenatally exposed to DEX. Widespread alterations in gene expression in diverse systems were observed, including catecholamine biosynthesis (DDC, PNMT), stress proteins (HSP27, HSP68, HSP70) and oxidative stress. These global changes induced by elevated fetal glucocorticoids suggest altered adrenal function may contribute to the pathogenesis of fetal programming of adult diseases.