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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) 110120 and 130140 (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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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. [Abstract] [Full Text] [PDF] |
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