DIRECT ADMINISTRATION OF INSULIN-LIKE-GROWTH-FACTOR TO FETAL RHESUS-MONKEYS (MACACA-MULATTA)

A potential treatment for the amelioration of fetal growth failure is insulin-like growth factor-I (IGF-I). To address concerns of safety an d efficacy, IGF-I (80 mu g/kg; GroPep Pty.) was administered ip to hea lthy rhesus monkey fetuses via ultrasound guidance every other day bet ween gestational days (GD) 110-120 and 130-140 (third trimester; term = approximately GD 165 +/- 10; n = 6). Pregnancies were monitored sono graphically, and fetal/maternal blood samples were collected for compl ete blood counts, immunophenotyping, and biochemical analyses. Blood s amples, external measures of the fetus and newborn, and tissue and org an weights were collected at fetal necropsy (GD 150; n = 2) or at term delivery of neonates (GD 160; n = 4). The results of these investigat ions have shown no evidence of hypoglycemia in the fetus or dam during the course of treatment. Circulating concentrations of fetal, but not maternal, IGF-I increased with treatment (similar to 80 to similar to 1015 ng/ml), and there was no evidence of a change in serum IGF-II or an increase in IGF binding protein-3 compared with historical control values. Fetal lymphocytes and select red cell parameters increased, a nd a significant elevation in circulating B cells and CD4/CD8 ratios i n fetal lymph nodes was shown. Although no changes were detected in bo dy weights, increases in thymic, splenic, and kidney weights and small intestine lengths occurred. Thus, administration of IGF-I to the feta l monkey is safe and results in 1) transient increases in circulating IGF-I, 2) a significant effect on fetal hematopoietic and lymphoid tis sues, and 3) an increase in select fetal organ weights and measures. T hese data suggest that IGF-I may represent a potential candidate for t herapeutic treatment of growth-compromised human fetuses in utero.