Transplacental effects of cortisone acetate on calcification and ossification of long bones in mice.

The transplacental effects of cortisone acetate on the skeleton of neonatal mice has been investigated. Pregnant mice were injected intramuscularly with 0.75 mg cortisone acetate daily on days 11-19 of gestation. The mice were allowed to deliver and pups were weighed on days 1, 3, 5, 10, 15, 20 and 30 and compared to controls. Light microscopy of non-decalcified longitudinal sections of bones revealed mineral precipitates throughout the zone of hypertrophic cartilage most prominent on days 1, 3 and 5 and gradually disappearing on days 10-20. Transmission electron microscopy revealed intracellular calcification of maturing and hypertrophic chondrocytes in addition to abnormal calcification of the interstitial substance. Hydroxylapatite crystals were not necessarily associated with matrix vesicles. Scanning electron microscopy of long bones revealed a wide zone of calcified intercartilagenous matrix representing the calcified proliferating and hypertrophic zones. In this area, the calcospherites varied in size (0.5-1.4 mu in diameter) and were found in both longitudinal and transverse septa. No significant differences in the distribution and shape of cartilage matrix vesicles between experimental and control animals was observed. However, the fact that mineral crystals in experimental animals was not necessarily associated with matrix vesicles points to the possibility that this "pathological calcification" may utilize a different mechanism than the normal process through matrix vesicles.