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Abstract-Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527Ϯ509 versus 28 050Ϯ561, PϽ0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six-to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380Ϯ587) compared with control rats (PϽ0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension. Key Words: glucocorticoids Ⅲ hypertension, gestational Ⅲ glomerular filtration rate Ⅲ kidney G lucocorticoids are often administered to pregnant women to accelerate fetal pulmonary maturation and prevent respiratory distress syndrome. 1-4 However, there is evidence that prenatal administration of steroids may have adverse effects on the developing fetus with consequences in later life. 5-9 Daily administration of prednisone, used as a treatment for infertility in humans, resulted in infants that are small for gestational age. 5 Similar findings have been demonstrated in rodents. [5][6][7] Administration of dexamethasone to pregnant rats produces adverse effects on the developing kidney. 6,7,9 Rats born to pregnant animals that received daily dexamethasone throughout gestation had a 50% reduction in the number of nephrons and a 30% reduction in glomerular filtration rate when they were studied at 60 days of age. 7 Rats exposed to daily steroids during development also had significant hypertension at 2 months of age. 6,7 Similarly, offspring of ewes given prenatal glucocorticoids have hypertension as adults. 10 -14 However, rats that were the product of mothers receiving daily steroids had severe intrauterine growth retardation, which is also a predisposing factor for the development of hypertension and renal disease in later life. [15][16]...

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This study shows that two daily doses of prenatal dexamethasone (0.2 mg/kg body weight) in rats do not produce intrauterine growth retardation. Adult offspring of rats that received prenatal dexamethasone during specific times of gestation have a reduced number of nephrons and hypertension.

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