Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation

Abstract

Treatment of nine pregnant Merino ewes (64.0 +/- 0.4 days of gestation) with dexamethasone (D; 0.76 mg/h for 48 h) resulted in significant alterations in fetal fluids compared with eight saline-infused control animals (S; 63.0 +/- 0.9 days). There was a substantial increase in allantoic fluid volume (177 +/- 18 ml, D vs. 31 +/- 6, S) but no change in amniotic fluid volume (248 +/- 12 ml, D; 305 +/- 24, S). For allantoic fluid there was a significant decrease in osmolality (213 +/- 4 mosmol/kg water, D; 230 +/- 5, S) and alterations in composition. Amniotic fluid osmolality was unchanged (292 +/- 2 mosmol/kg water, D; 293 +/- 1, S), but amniotic fluid composition was affected. In four fetuses in which bladder and amniotic cannulas were inserted at gestational age 68-75 days, fetal urine flow rate increased from a mean of 4.1 +/- 1.1 to 13.8 +/- 2.6 ml/h after 24 h and 11.8 +/- 3.0 ml/h at 48 h for a similar maternal D infusion, whereas no such increase occurred in four control fetuses. All the fetal urine voided during a 3.5- to 4-h infusion of 51Cr-labeled EDTA into the fetal bladder was directed to the allantois. The results suggest that the increase in allantoic fluid volume resulted from increased fetal urine output into the allantoic compartment, although the composition of the excess allantoic fluid differed substantially from that of fetal urine. There was a greater incidence of abnormal cotyledons in the D-infused ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antenatal Dexamethasone: Effect on Ovine Placental 11β-Hydroxysteroid Dehydrogenase Type 2 Expression and Fetal Growth

“…Synthetic glucocorticoids, such as dexamethasone, are poorly metabolized by 11␤-HSD-2 (22)(23)(24), enabling them to cross the placenta into the fetal compartment (25)(26)(27)(28). Limited studies in sheep have demonstrated the growth-retarding effects of single and multiple courses of antenatal glucocorticoids (29 -31).…”

Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

“…Administration of dexamethasone for 48 hours between 64-66 days of gestation (term=145-150 days) resulted in generally larger cotyledons with overgrowth of the fetal tissue when the placenta was examined at completion of the infusion [105]. However, this was not observed in other studies using betamethasone later in gestation (around 100 days of gestation) [108].…”

“…The effects of excess maternal glucocorticoid exposure, on placental growth and development, has been investigated using a range of animal models including the sheep [105][106], rat [85], mouse [107] and spiny mouse [66]. Most of these studies have utilised synthetic glucocorticoids (namely dexamethasone or betamethasone) and been designed to mimic the level of exposure experienced by the preterm infant.…”

Cortisol Infusion Decreases Renin, But Not PGHS-2, EP2, or EP4 mRNA Expression in the Kidney of the Fetal Sheep at Days 109–116

“…In the sheep, glucocorticoid administration very early in gestation results in a reduction in sodium and chloride excretion from the mesonephric kidney (24). However, by d 64, when the mesonephric kidney is no longer functional and the metanephric kidney is actively synthesizing RAS proteins and producing urine, dexamethasone administration increased fetal urine flow rate (10). Later, at 114 d gestation, acute (4 h) intrafetal cortisol infusion increased GFR, and decreased proximal tubule sodium reabsorption, resulting in diuresis and natriuresis (12).…”

“…It is clear from several studies that the RAS also plays an important role in renal development and function in the fetus (8,9). Although bilateral adrenalectomy has no apparent effect on fetal renal function until d 142 of gestation because of placental-maternal exchange mechanisms that maintain fetal electrolyte and fluid balance (3), infusion of cortisol increases allantoic fluid volume at 64 d (10) and may mature the fetal kidney (11), whereas acute administration of cortisol to the immature fetal sheep kidney (at 114 d) leads to natriuresis and diuresis (12). These data suggest that cortisol has an effect on fetal kidney function or maturation.…”