The effect of prenatal indium chloride exposure on chondrogenic ossification

Daily indium chloride doses of control (0) or 400 mg/kg were administered o rally to pregnant Sprague-Dawley (SD) rats by gavage, on d 20 of gestation. Indium concentration was determined in the maternal and fetal blood, liver s, kidneys, skulls, and femurs by atomic absorption spectrometry. Further g roups of pregnant rats were treated with control (0) or 400 mg/kg indium ch loride orally, during the whole gestation period. The fetuses were examined on d 21 of gestation, using histological and histochemical methods. Four h ours after the administration indium concentration was found to be signific ant in the blood, liver, and kidneys of the dame. Twenty-four hours later i t increased in the blood but not in the liver and kidney. Fetal indium conc entrations were 40-50% of the maternal levels due to a barrier of the place nta. In the skull and the femur, indium was already detectable at 4 h after the administration, and by the end of 24 h, metal concentration was severa l rimes higher than that at 4 h, indicating accumulation. Furthermore, it w as found that the birefringency of collagen detectable by picrosirius red s taining in polarized light around the chondrocytes disappeared and became i rregular. In the matrix of the epiphyseal cartilage, the regular, birefring ent network demonstrable by Rivanol reaction became irregular and hardly re cognizable. In the cytoplasm of the chondrocytes, the diffuse, evenly distr ibuted positive Ricinus communis agglutinin reaction became irregular or di sappeared. Similar but much weaker changes were observed with concanavalin A and wheat germ agglutinin stainings. It was concluded that the missing fe mur and micromelia diagnosed by alizarin staining is the consequence of a s pecific toxic effect of indium that inhibits chondrogenic ossification. No similar histochemical changes were observed in the bones of the skull devel oping by desmogenic ossification, despite the presence of indium. Data indi cate that the mechanisms of the effects of indium causing retardation and/o r malformation differ in the bones developing through desmogenic or chondro genic ossification.