Fetal adrenal gland alterations in a rat model of adverse intrauterine environment

Bibeau K, Battista MC, Houde V, Brochu M. Fetal adrenal gland alterations in a rat model of adverse intrauterine environment. Am J Physiol Regul Integr Comp Physiol 298: R899-R911, 2010. First published November 28, 2009; doi: 10.1152/ajpregu.00238.2009.-By feeding a low-sodium diet to dams over the last third of gestation, we have developed an animal model of intrauterine growth restriction (IUGR). Given that fetal adrenal development and maturation occur during late gestation in rats, the aim of this study was to evaluate the expression of proteins and enzymes involved in steroidogenesis and catecholamine synthesis in adrenal glands from IUGR fetuses. A gene microarray was performed to investigate for alteration in the pathways participating in hormone production. Results show that increased aldosterone serum concentrations in IUGR fetuses were associated with higher mRNA adrenal levels of angiotensin II receptor type 1 (AT(1)R) and cytochrome P450 aldosterone synthase in response to decreased serum sodium content. Conversely, reduced serum corticosterone concentrations in these fetuses appear to result from alterations in gene expression involved in cholesterol metabolism, such as the augmented apolipoprotein E levels, and in steroidogenesis, like the decreased levels of cytochrome P45011 beta-hydroxylase. Furthermore, increased AT(2)R expression and the presence of hypoxia and oxidative stress may, in turn, explain the higher adrenal mRNA levels of enzymes involved in catecholamine synthesis. Despite this increase, catecholamine adrenal content was reduced in males and was similar in females compared with sex-matched controls, suggesting higher catecholamine secretion. This could be associated with the induction of genes involved in inflammation-related, acute-phase response in IUGR fetuses. All of these alterations could have long-lasting health effects and may, hence, be implicated in the pathogenesis of increased blood pressure and cardiac hypertrophy observed in IUGR adult animals from this model.