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

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(OH₂D₃ 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(H)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.