Induction of Skeletal Malformations in the Offspring of Rats Fed a Zinc Deficient Diet

Abstract

Pregnant rats were subjected to a trace metal poor diet (1.2 ppm zinc, 5.9 ppm copper, 40 ppm manganese) during the entire gestation. The rat mothers did not gain weight during pregnancy and showed decreased liver weight and lowered serum glucose levels on gestational day 20. The offspring exhibited decreased body and placental weights, delayed ossification of the skeleton, and an increased resorption rate. We also found 4% skeletal malformations in the offspring (0% in the controls), which closely resembled a type of malformation previously encountered in rats when the mother was manifest diabetic (i.e. sacral dysgenesis). The zinc levels were decreased and manganese levels increased to the same extent in offspring of trace metal restricted (this study) and manifest diabetic rats (previous studies). Furthermore, when pregnant rats on the trace metal restricted diet were resupplemented with 75 ppm zinc in the drinking water the offspring largely normalized their somatic and placental growth, skeletal maturation, as well as their zinc and manganese levels. In addition, the fetuses of the zinc resupplemented rats did not show any malformations. The possibility of common teratological mechanisms in maternal diabetes and trace metal deficiency may therefore be considered.