Skeletal Growth in Fetal Rats: Effects of Glucose and Amino Acids

The modified hyperglycemia-hyperinsulinism hypothesis, which characterizes intrauterine growth of diabetic pregnancy, was studied in fetal rats. From day 19 to day 21 postconception, pregnant rats were constantly infused with saline, amino acids, or glucose. In the fetus, serum somatomedin activity was determined, with the porcine bioassay and the incorporation of ³H-thymidine into rib cartilage and isolated chondrocytes in vivo in response to serum from normal maternal or fetal rats. In comparison with control fetuses, body weights were decreased in glucose-exposed fetuses (4.66 ± 0.25 versus 3.75 ± 0.99, N = 121; P < 0.001), and increased (4.87 ± 0.57, N = 105; P < 0.05) in amino acid-exposed fetuses. Serum somatomedin activity (U/ml) was higher in glucose-treated (0.79 ± 0.40, N = 11; P < 0.05) and amino acid-treated animals (0.90 ± 0.16, N = 10; P 0.001) than in controls (0.55 ± 0.04, N = 13). In vivo labeling with thymidine resulted in a higher radioactivity of cartilage in small fetuses compared with large fetuses when the dams had been infused with saline (r = –0.531, N = 56; P < 0.001) or amino acids (r = –0.292, N = 52; P < 0.01). Opposite results were obtained in hyperglycemie animals (r = 0.542, N = 54; P < 0.001). When isolated chondrocytes were incubated with serum from. normal fetal rats, the incorporation of thymidine was about 10 times higher into cells from small fetuses than from large fetuses, irrespective of the infusion regimen. In parallel experiments chondrocytes from the same cell pool were incubated with serum from normal pregnant rats. In these experiments the isotope incorporation into chondrocytes was enhanced in small and large fetuses from saline- or amino acid-treated mothers. In contrast, the thymidine incorporation into isolated chondrocytes from small hyperglycemie fetuses was significantly inhibited by normal maternal serum. The results confirm the many observations in fetal rats that a moderate or severe hyperglycemia during pregnancy decreases fetal body weight and that an increased somatomedin activity, as measured with adult tissues (such as in the porcine bioassay), may not be associated with increased body weight or length. Second, it appears that the growth-promoting activity of fetal serum differs from that of adult serum. Third, similar to adult hyperglycemie rats, an inhibition of the thymidine incorporation into cartilage of small hyperglycemie fetal rats was Observed.