| Research Abstract |
1. Insulin-like growth factor-I and its binding proteins (IGFBPs) regulate placental transport function. Expression of IGFBPs translocate from syncytiotrophoblast to cytotrophoblast at early stage of gestation corresponding to differentiation of placental function. Only IGFBP-2 mRNA was expressed predominantly in rat placenta throughout gestation.
2. All four IGFBPs including IGFBP-1, -2, -3, and -4 were identified in fetal circulation throughout pregnancy by Western ligand blot. In contrast to maternal circulation, there was no protease activity in fetal circulation. However, levels of these IGFBPs varied corresponding to fetal growth such as IUGR,giant and preterm infants. Especially, levels of IGFBP-2 were extremely increased in infants with IUGR.Since IGFBP-2 regulates IGF-II rather than IGF-I,this result indicates that physiological significance of IGF-II in fetal growth should be reevaluated.
3. We have demonstrated that fetal acidosis due to hypoxia is correlated with endothelin-1
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(ET-1) elevation in the fetal circulation. Furthermore, ET-1 gene expression in the rat placenta was augmented two-fold in response to chronic hypoxic stress to the fetus by unilateral ligation of the uterine artery. In an assessment of the fetal systemic circulation, it was possible to record fetal central venous pressure pulse waveforms (CVPW) noninvasively by newly developed measurement of pulsatile changes in vessel diameter. On the CVPW,four waves which were corresponding to right atrial contraction, right ventricular contraction, opening and closure of tricuspid valve were identified from correlation of the fetal electrocardiogram. The newly noninvasive analysis in the degree of right cardiac afterload and cardiac dysfunction was established.
From these results, Pathogenesis of IUGR is pathophysiologically originated from reduced nutritional transfer due to impaired placental exchange in which maladaptation of trophoblast implantation resulted in placental malfunction. Furthermore, it has been elucidated that IGF-I and IGFBPs regulated by interaction between chorion and decidua control placental transport function and that growth and maturation of fetus is regulated by fetal own IGFBPs. On the other hand, ET-1, expressed in the chorionic villi, might be involved in the blood shift from the placenta to the fetal systemic circulation upon fetal hypoxia. The response in the fetal systemic circulation that occur in association with fetal compromise was associated with right cardiac afterload and influenced by the CVPW.The newly developed noninvasive measurement of vessel diameter changes makes it possible to apply for clinical evaluation. Less
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