Impaired osteogenesis in the fetus induced by administration of cortisone to pregnant mice

Pregnant mice were treated during days 11 to 19 of gestation with daily i.m. injections of 1 mg cortisone acetate. Fetuses were removed on day 20 of gestation. The cortisone treated mothers showed a smaller gain in weight than control mice injected with saline solutions. A higher percentage of fetuses underwent resorption in experimental than in control animals. The fetuses of the cortisone treated animals weighed less than those of the control animals and cleft palate was present in 22.7% of them. The femurs and tibias of the experimental fetuses were shorter than those of the controls, due mainly to shortening of the diaphysis, whereas the epiphysis showed little, if any, difference. The main histologic findings were narrowing of the zone of hypertrophic cartilage in the epiphysis, disorganization of metaphyseal trabeculae, thinning of the subperiosteal diaphyseal bone forming the wall of the marrow cavity, thinning of bone trabeculae and widening of the marrow cavity. The preosteoblasts and osteoblasts were reduced in number in both the metaphysis and diaphysis, while the osteoclasts were increased. It is concluded that cortisone has a transplacental effect on the fetal skeleton in mice, primarily by decreasing bone formation.