Ovine feto-placental metabolism

Abstract

Fetal growth depends on the transplacental nutrient supply, which, in turn, is determined partially by the consumption and production of nutrients by the uteroplacental tissues. In fetal sheep, the rates of growth and umbilical glucose uptake decline coincidently towards term in parallel with the normal prepartum rise in plasma cortisol. While cortisol is known to reduce growth in fetal sheep, its effects on the uteroplacental handling and delivery of nutrients remain unknown. Hence, this study, quantified the rates of umbilical uptake and uteroplacental consumption of nutrients in preterm fetuses infused with cortisol for 5 days to mimic the prepartum cortisol surge. Umbilical uptakes of glucose and lactate, but not oxygen, were significantly lower in cortisol- than saline-infused fetuses, irrespective of whether values were expressed as absolute or weight-specific rates. The rate of uteroplacental consumption of glucose, but not oxygen, was significantly higher in cortisol- than saline-infused animals. Absolute rates of uteroplacental lactate production were lower in cortisol-infused animals. When all data were combined, fetal plasma cortisol levels were positively correlated to uteroplacental glucose consumption and inversely related to umbilical glucose uptake. Cortisol treatment had no apparent effect on placental mRNA expression for the glucose transporters, GLUT-1 and GLUT-3. The results demonstrate that cortisol is physiological regulator of uteroplacental metabolism and nutrient delivery to the sheep fetus. These observations have important implications for fetal growth both in late gestation and during adverse intrauterine conditions, which raise fetal cortisol levels earlier in gestation.

Figure 1. Rates of (A) umbilical uptake and (B) uteroplacental consumption or production of glucose (i) lactate (ii) and oxygen(iii)

Rates were expressed as weight-specific values (μmol min⁻¹ kg⁻¹) per kg fetal weight (A) or kg placenta (defined as total placentome mass) (B). Fetuses were infused with either saline (n = 8) or cortisol (n = 8). Significant differences are: *P < 0.02; ^†P < 0.05; ^‡P < 0.039 (Student's unpaired t test).

Figure 2. Relationships between the fetal plasma cortisol concentration (ng ml⁻¹) and either umbilical glucose uptake (A) or uteroplacental glucose consumption (B)

Uptake expressed in μmol min⁻¹ (kg fetus)⁻¹; y =–0.162x+ 35.374, n = 16, r = 0.52, P < 0.037); consumption expressed in μmol min⁻¹ (kg placenta)⁻¹; y = 4.232x+ 174.520, n = 16, r = 0.60, P < 0.014). Fetuses were infused with either saline (•, n = 8) or cortisol (○, n = 8).

Figure 3. The effects of cortisol on the distribution of nutrients

The mean (± s.e.m.) percentage distribution of the uterine uptake of glucose and oxygen between fetal (black columns) and uteroplacental tissues (grey columns) and of uteroplacental lactate production between fetal (black columns) and maternal tissues (grey columns) in saline- (n = 8) and cortisol-infused fetuses (n = 8). *P < 0.008, compared to saline-infused controls (Student's unpaired t test). 100%= total uterine uptake or uteroplacental production, irrespective of absolute value.

Figure 4. The effect of cortisol on placental GLUT expression

In situ hybridization analysis of GLUT-1 and GLUT-3 mRNA expression shown as typical sections through placentomes from cortisol- and saline-infused fetuses visualized with the sense and antisense oligionucleotide probes (A) and mean (± s.e.m.) values of integrated optical density (IOD) units of placentome sections from saline- (n = 4) and cortisol-infused fetuses (n = 4) (B).