FETAL AND NEONATAL DEVELOPMENT OF ANTITHROMBIN-III PLASMA ACTIVITY AND LIVER MESSENGER-RNA LEVELS IN SHEEP

In healthy term human newborns a unique hemostatic balance exists with reduced plasma concentrations of several coagulant and anticoagulant proteins, including antithrombin III (AT III). In preterm newborns eve n lower AT III concentrations are observed, with an associated thrombo embolic risk. As part of our study program on the gene regulation of A T III, we investigated whether the increase in plasma AT III activity during fetal and neonatal development is particularly controlled at th e transcriptional level. Plasma AT III activity and liver AT III mRNA content between the 8th wk of gestation and the 4th wk after birth wer e determined in sheep. AT III activity gradually increased from 34% of the mean adult level at 8-10 wk of gestation to 86% (2.5-fold) at ter m (21 wk), and remained in the adult range after birth. The mean body weight, and thus plasma volume, increased 57-fold. Therefore, the tota l plasma AT III activity increased 140-fold. The total liver AT III mR NA content increased only 14-fold between these fetal stages, mainly d ue to increased liver weight. Therefore, the total plasma AT III activ ity increased 10-fold more than the liver AT III mRNA content. In the neonatal period between d 1-3 and 28, the total plasma AT III activity increased only 2-fold more than the liver AT III mRNA content. We con clude that the increase in plasma AT III activity during the fetal per iod, and similarly the neonatal period, is not regulated at the transc riptional level. Furthermore, a unique fetal isoform of AT III was det ected in sheep. This isoform had a 2500-D higher molecular mass compar ed with the other fetal, neonatal, and adult AT III isoform, and disap peared from the circulation between d 2 and 7 after birth. These AT II I isoforms differ in their carbohydrate moiety.