Transplacental effects of 1,25-dihydroxycholecalciferol and of 24,25-dihydroxycholecalciferol on the limb skeleton of fetuses and offspring rats.

Abstract

The transplacental effects of 1,25(OH)2D3 and of 24,25(OH)2D3 on bone formation in rat fetuses and pups have been investigated. Pregnant rats treated with 1,25(OH)2D3 or with 1,25(OH)2D3 and 24,25(OH)2D3 showed hypercalcemia, while those treated with 24,25(OH)2D3 did not. Fetal weight was markedly reduced by treatment with 1,25(OH)2D3 and not with 24,25(OH)2D3 or with a combination of both metabolites. Microscopical examination of fetal long bones showed after treatment with 1,25(OH)2D3 a marked reduction in diaphysial length. Diaphyseal trabeculae were thin and disorganized. The epiphysis had a thinner layer of hypertrophic and calcified cartilage. The numbers of osteoclasts in the diaphysis and metaphysis were the same as in controls. Treatment with 24,25(OH)2D3 did not affect fetal bone length; many bone trabeculae were found in the diaphyseal cavity leaving small bone marrow spaces; the number of osteoclasts in the metaphysis and in the diaphysis was increased. All changes in the skeleton disappeared during the first week after birth. It can be suggested that high doses of 1,25(OH)2D3 inhibit bone formation and maturation of cartilage. The addition of 24,25(OH)2D3 to 1,25(OH)2D3 seemed to reduce the toxic effects of the latter on the fetal skeleton. These results point to a definite difference between the action of high doses of 1,25(OH)2D3 and 24,25(OH)2D3 on fetal bone.