Prolonged low-dose dexamethasone, in early gestation, has no long-term deleterious effect on normal ovine fetuses.
Low-dose dexamethasone (D) treatment is used in pregnancies where the fetus is suspected to be at risk of congenital/virilizing adrenal hyperplasia. To study if this treatment had any immediate or long-term effects in normal fetuses, pregnant ewes were treated with D (20 microg/kg maternal body weight x d) or saline (S), from d 25-45 of gestation. Tissue was collected from fetuses killed at 45 d (S = 6; D = 8), 130 d (S = 8; D = 8), or lambs at 2 months of age (S = 6; D = 6) and mRNA levels measured using real-time PCR. D treatment reduced adrenal wt at 45 d (S, 12.2 +/- 0.7 mg; D, 6.3 +/- 0.4 mg) and significantly decreased adrenal mRNA for P(450scc). At 130 d, fetuses from the D treatment were growth retarded (S, 3.2 +/- 0.1 kg; D, 2.5 +/- 0.1 g), but the adrenals were appropriate for the body weight. mRNA levels of angiotensinogen, the AT(1) receptor and mineralocorticoid receptor (MR) and GR were similar in kidney and brain (hypothalamus, hippocampus, medulla oblongata) except for hippocampal expression of MR and GR, which was significantly decreased by D treatment. By 2 months, BW and hippocampal MR and GR mRNA levels were similar, and lambs were normotensive (S, 83 +/- 3 mm Hg; D, 78 +/- 3 mm Hg). Thus, there were no persistent, long-term effects of prolonged low-dose D treatment in normal ovine fetuses.
Moritz
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Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville 3052, Victoria, Australia. k.moritz@hfi.unimelb.edu.au
Butkus
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Hantzis
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Peers
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Wintour
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Dodic
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D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002138:Calibration; D017931:DNA Primers; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D017931:DNA Primers; D012333:RNA, Messenger; D003907:Dexamethasone