Placental glucose transport in growth-restricted pregnancies induced by overnourishing adolescent sheep

Abstract

Glucose clamp procedures were used to determine whether the slowing of fetal growth during the final third of gestation in overnourished adolescent ewes is due to a reduction in placental glucose transport capacity. Singleton pregnancies to a single sire were established by embryo transfer and thereafter adolescent dams were offered a high (n = 11) or moderate (n = 7) nutrient intake. Studies were conducted at 130 +/- 0.5 days gestation. Uterine and umbilical blood flows were studied by the steady-state transplacental diffusion technique and glucose fluxes quantified by the Fick principle. To determine the relationship between the transplacental glucose gradient and umbilical (fetal) glucose uptake, studies were conducted with maternal arterial glucose clamped at 5 micromol ml(-1) and fetal glucose at spontaneously occurring and two additional higher levels. Maternal body weight gain during gestation averaged 282 and 57 g day(-1) for high- and moderate-intake dams, respectively. Total placentome weight (209 +/- 23 vs. 386 +/- 34 g) and fetal weight (3072 +/- 266 vs. 4670 +/- 196 g) were lower (P < 0.001) in high- than in moderate-intake groups. The growth-restricted pregnancies in the high-intake dams were associated with reduced uterine (P < 0.05) and umbilical (P < 0.02) blood flows and, in the non-perturbed state, the fetuses were relatively hypoxic (2.1 vs. 3.0 micromol ml(-1), P < 0.05) and hypoglycaemic (0.90 vs. 1.31 micromol ml(-1), P < 0.002). Linear regression analysis of umbilical glucose uptake at three steady-state uterine-umbilical arterial transplacental plasma glucose concentration gradients revealed that absolute placental glucose transport capacity was lower in high- than in moderate-intake dams (mean slope, 0.8 vs. 1.5 dl min(-1), P < 0.05; and mean intercept, 1.84 vs. 3.40 micromol ml(-1)). However, glucose transfer capacity was not different between the two groups when expressed on a placental weight-specific basis. This confirms that the small size of the placenta per se is the major limitation to placental glucose transfer in the overnourished adolescent pregnant sheep.

Figure 1

Weekly dry matter intakes from embryo transfer on day 4 of the cycle until day 119 of gestation in singleton-bearing adolescent dams offered a high (□) or moderate (▪) nutrient intake. In this and subsequent figures, values are given as means ± s.e.m.; where error bars are not shown, they are smaller than the symbol size.

Figure 2

Relationships between total placentome mass and fetal brain (A), liver (B) and body (C) weight in fetuses from adolescent dams offered a high (□) or moderate (▪) nutrient intake throughout pregnancy.

Figure 3

Relationships between umbilical glucose uptake and the transplacental plasma arterial glucose concentration difference in adolescent dams offered a high (□) or moderate (▪) nutrient intake throughout pregnancy. See text for linear regression equations.

Figure 4

Relationships between umbilical glucose uptake per kilogram fetus and the transplacental plasma arterial glucose concentration difference in adolescent dams offered a high (□) or moderate (▪) nutrient intake throughout pregnancy. For high-intake pregnancies, y = −0.68 + 0.272x. For moderate-intake pregnancies, y = −0.78 + 0.327x.

Figure 5

Relationships between umbilical glucose uptake per kilogram placenta and the transplacental arterial glucose concentration difference in adolescent dams offered a high (□) or moderate (▪) nutrient intake throughout pregnancy.