Abstract
Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment.
Highlights
In clinical practice, synthetic glucocorticoids, such as dexamethasone, are administered routinely to pregnant women at risk of preterm delivery in order to promote fetal maturation and neonatal survival [1, 2]
The effect of maternal dexamethasone treatment, in a regime similar to that used in clinical practice, on the components of the reninangiotensin system (RAS) in the pregnant mother and fetus during late gestation is unknown in any species
Pulmonary angiotensin-converting enzyme (ACE) mRNA and ACE concentration were significantly greater in the fetuses exposed to dexamethasone compared to the control fetuses (Figure 2A, P Ͻ .05)
Summary
Synthetic glucocorticoids, such as dexamethasone, are administered routinely to pregnant women at risk of preterm delivery in order to promote fetal maturation and neonatal survival [1, 2]. These drugs mimic the normal rise in endogenous glucocorticoids seen in the fetus near term by promoting structural and functional changes in fetal tissues in preparation for life after birth [3]. The study hypothesized that synthetic glucocorticoid administration to the pregnant ewe would stimulate components of both the maternal and fetal RAS with potential consequences for fetal development
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