Studies on the role of vitamin D in early skeletal development, mineralization, and growth in rats

The effects of vitamin D deficiency on fertility, reproductive capacity and on fetal and neonatal development were investigated. Female weanling rats were maintained on either a vitamin D-replete or vitamin D-deficient diet until maturity and mated with normal males. Vitamin D-deficient females were capable of reproduction. However, vitamin D deficiency reduced overall fertility by 75%, diminished litter sizes by 30% and impaired neonatal growth from day 6 to day 15 of lactation. Fetal development asjudged by weight gain and viability appeared normal. Neonatal viability was also normal even though growth was retarded. The concentrations of calcium and inorganic phosphate in milk from vitamin D-replete and vitamin D-deficient mothers were similar implying that the transfer of calcium and phosphorus from the plasma to the milk is a vitamin D-independent process.

The kidneys are thought to be the only organs capable of 1 alpha-hydroxylation of vitamin D and its metabolites. We have examined the in vivo conversion of 3H-(25,26)-25-hydroxyvitamin D3(25OHD3) to 3H-(25,26)-1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in vitamin D-deficient, pregnant and nonpregnant rats. As expected, nephrectomy of nonpregnant, vitamin D-deficient rats prevented the conversion of 25OHD3 to 1 alpha,25(OH)2D3. In contrast, nephrectomy of pregnant, vitamin D-deficient rats reduced but did not abolish the formation of 1 alpha,25(OH)2D3 from its precursor. The identity of the radioactive metabolite formed from 3H-25OHD3 which circulated in nephrectomized, pregnant rats was established as 1 alpha,25(OH)2D3 by comigration with synthetic 1 alpha,25(OH)2D3 on high-pressure liquid chromatography. The simultaneous absence of 1 alpha,25(OH)2D3 in the fetal kidneys indicated that the site of 1 alpha-hydroxylation after nephrectomy of the pregnant rat was probably extra-renal in origin. Two sites of 1 alpha-hydroxylation of 25OHD3, one renal and the other extra-renal, either fetoplacental or maternal, may exist in the pregnant, vitamin D-deficient rat.