Effects of prenatal exposure to manganese on postnatal development and behavior in mice:: Influence of maternal restraint

Abstract

Manganese (Mn) is an essential trace element whose deficiency and excess have been reported to cause central nervous system (CNS) disturbances. On the other hand, during pregnancy, maternal stress has been shown to enhance the developmental toxicity of a number of metals. In this study, the maternal toxicity and developmental effects of a concurrent exposure to Mn and restraint stress were evaluated in mice. Pregnant animals were divided into three groups and received subcutaneous injections of manganese chloride tetrahydrate (MnCl 2·4H 2O) at 0, 1 and 2 mg/kg/day on Gestation Days 6–18. Each group was divided into two subgroups. Mice in one subgroup were subjected to restraint for 2 h/day on Days 6–18 of gestation. Pregnant mice were allowed to deliver, and pups were evaluated for physical and neuromotor maturation. Subsequently, adult mice were also evaluated for activity and learning. A significant increase in perinatal mortality was observed at 2 mg/kg/day Mn. A delay in some developmental landmarks (eye opening, testes descent) due to Mn exposure (2 mg/kg/day) was also seen in both restrained and unrestrained animals. No differences in motor resistance and coordination, or in learning at the passive avoidance test, were noted in adult mice. At the current Mn doses, combined exposure to Mn and stress during the prenatal period did not produce long-lasting effects on adult mice.