Treatment of growth-restricted fetuses with insulin-like growth factors (IGFs) is a potential method for ameliorating growth failure prior to irreversible, long-term damage. However, little is known regarding effect(s) of IGF when administered directly to the fetus. In both human and nonhuman fetal primates, serum IGF levels increase with advancing gestation, and alterations in this developmental profile have been correlated with abnormal growth patterns and intrauterine growth restriction (IUGR). To assess safety and efficacy, IGF-I (80 mg/kg; GroPep Pty, Ltd) was administered intraperitoneal (IP) to normally-grown rhesus fetuses via ultrasound guidance every other day from gestational day (GD) 110-120 and from GD 130-140 (third trimester; term ~GD 165110; N=6). Pregnancies were monitored sonographically and standard biometrics evaluated. Fetal and maternal blood samples were collected periodically during the treatment period for complete blood counts (CBCs), immunophenotyping, and biochemical analyses. On the day of fetal tissue harvest (GD 150), maternal and fetal blood samples were collected, and external fetal measures and body and organ weights were assessed. These investigations show normal CBCs and no evidence of hypoglycemia in fetus or dam. Circulating concentrations of fetal, but not maternal, IGF-I increased with treatment, although there were no changes in serum IGF-II or IGF binding proteins (IGFBPs) compared to historical controls. Additionally, increased thymic weights and total T-and B-cells were noted in treated fetuses. These studies suggest that the increase in free IGF-I in the absence of elevated IGFBPs may prove advantageous under growth-compromised conditions in which more IGF-I would be bioavailable to essential tissues during critical stages of development. Fetal supplementation with IGF-I during appropriate period(s) of gestation is proposed as a method for reversing growth failure due to its growth and anabolic actions. *KEY*Fetal growth, Fetal treatment, IGF-I
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