The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat

The insulin-like growth factor (IGF) axis, a key regulator of embryonic growth and development, is exquisitely sensitive to the nutrient status of the animal. In addition to macronutrient deficiencies, zinc deficiency can impact the IGF axis. Gestational zinc deficiency is teratogenic, resulting in intrauterine growth retardation and structural abnormalities. The aim of this study was to investigate the effects of gestational zinc deficiency on the fetal IGF axis in a rat model. From gestation day (GD) 0.5, dams consumed zinc-deficient (ZD, 0.3 mg zinc/kg) or control (25 mg zinc/kg) diet ad libitum, while a third group of dams consumed the control diet in amounts equivalent to the food intake of the ZD dams (Paired group). On GD 19.5 fetal tissue, blood and amniotic fluid were collected. Fetal growth was significantly reduced by zinc deficiency compared with the Paired and Control groups. Fetuses from the Paired group were smaller compared with the Control, but only ZD fetuses had structural malformations. Amniotic fluid IGF-1 concentrations were significantly lower in the Paired group than in the ZD and Control groups. Plasma of ZD fetuses contained lower levels of IGF binding protein-1 when compared with fetuses in the Paired and Control groups. Fetal liver IGF-1 mRNA levels were lower in the ZD fetuses than in the Paired and Control fetuses. These observations suggest that differences in the fetal IGF axis between ZD and Paired groups contribute to the poor pregnancy outcome and enhanced fetal growth retardation observed with zinc deficiency.