Role of fetal 1,25-dihydroxyvitamin D production in intrauterine phosphorus and calcium homeostasis

During intrauterine life, fetal mineral accretion depends on active transfer from mother to fetus by the placenta. To evaluate the role of fetal production of 1,25-dihydroxyvitamin D in regulation of fetal phosphorus, calcium, and parathyroid homeostasis, studies were performed in ewes and their fetal lambs. Fetal nephrectomy caused a rise in fetal serum phosphorus and a fall in total calcium 5 days after nephrectomy. Fetal blood ionized calcium also fell and serum parathyroid hormone rose. In sham-nephrectomized fetuses, all four measurements were unchanged compared to control values. Simultaneous maternal values of ionized calcium were normal in control and nephrectomized fetuses. Fetal ureteral severance and drainage of urine into the fetal peritoneal cavity produced none of the effects of fetal nephrectomy. Daily intravenous injection of 1,25-dihydroxyvitamin D into fetuses after nephrectomy prevented the rise in serum phosphate, and serum calcium did not fall. The results suggest that fetal 1,25-dihydroxyvitamin D regulates fetal phosphate homeostasis, perhaps by the placenta, which in turn regulates blood-ionized calcium concentration.