Maternal dexamethasone treatment alters tissue and circulating components of the renin-angiotensin system in the pregnant ewe and fetus

Alison J. Forhead, Juanita K. Jellyman, Miles J. De Blasio, Emma Johnson, Dino A. Giussani, Fiona Broughton Pipkin, Abigail L. Fowden

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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 pregnanteweandfetus.From125 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 secondinjection, 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 renalrenin,orAIItype1or2receptorsinthelungsandkidneys;orinpulmonary,renalorcardiacprotein 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.

Original languageEnglish
Pages (from-to)3038-3046
Number of pages9
JournalEndocrinology
Volume156
Issue number8
DOIs
Publication statusPublished - 1 Aug 2015
Externally publishedYes

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