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Endocrinology Vol. 138, No. 8 3349-3358
Copyright © 1997 by The Endocrine Society


ARTICLES

Direct Administration of Insulin-Like Growth Factor to Fetal Rhesus Monkeys (Macaca mulatta)1

Alice F. Tarantal, Maya K. Hunter and Sharron E. Gargosky2

California Regional Primate Research Center and the Department of Pediatrics, University of California (A.F.T.), Davis, California 95616; and the Department of Pediatrics, Oregon Health Sciences University (M.K.H., S.E.G.), Portland, Oregon 97201

Address all correspondence and requests for reprints to: Alice F. Tarantal, Ph.D., California Regional Primate Research Center, University of California, Davis, California 95616-8542. E-mail: aftarantal{at}ucdavis.edu

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 µg/kg; GroPep Pty.) was administered ip 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 (~80 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, 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.




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Am. J. Physiol. Endocrinol. Metab.Home page
E. R. Lumbers, M. y. Kim, J. H. Burrell, V. Kumarasamy, A. C. Boyce, K. J. Gibson, K. L. Gatford, and J. A. Owens
Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep
Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E513 - E519.
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Copyright © 1997 by The Endocrine Society