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 and efficacy, IGF-I (80 microg/kg; GroPep Pty.) was administered i.p. to healthy rhesus monkey fetuses via ultrasound guidance every other day between gestational days (GD) 110-120 and 130-140 (third trimester; term = approximately GD 165 +/- 10; n = 6). Pregnancies were monitored sonographically, and fetal/maternal blood samples were collected for complete blood counts, immunophenotyping, and biochemical analyses. Blood samples, external measures of the fetus and newborn, and tissue and organ weights were collected at fetal necropsy (GD 150; n = 2) or at term delivery of neonates (GD 160; n = 4). The results of these investigations 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 (approximately 80 to approximately 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, and a significant elevation in circulating B cells and CD4/CD8 ratios in fetal lymph nodes was shown. Although no changes were detected in body weights, increases in thymic, splenic, and kidney weights and small intestine lengths occurred. Thus, administration of IGF-I to the fetal monkey is safe and results in 1) transient increases in circulating IGF-I, 2) a significant effect on fetal hematopoietic and lymphoid tissues, and 3) an increase in select fetal organ weights and measures. These data suggest that IGF-I may represent a potential candidate for therapeutic treatment of growth-compromised human fetuses in utero.
Tarantal
A F
AF
California Regional Primate Research Center and the Department of Pediatrics, University of California, Davis 95616, USA. aftarantal@ucdavis.edu
Hunter
M K
MK
Gargosky
S E
SE
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005865:Gestational Age; D016130:Immunophenotyping; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology; D008253:Macaca mulatta / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D009929:Organ Size; D011247:Pregnancy; D013154:Spleen / Q000033:anatomy & histology / Q000196:embryology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000196:embryology; D016216:Ultrasonography, Prenatal
D001786:Blood Glucose; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II