Effects of calcitonin gene deletion on fetal-placental calcium metabolism and maternal fertility

Abstract

Very little is known about how calcium metabolism is regulated in the fetus, and in particular, the role of calcitonin (CT) has not been established. We studied fetal mice in which the CT gene has been deleted to determine whether CT is critically required for normal fetal-placental calcium homeostasis and skeletal development. -- We demonstrated that homozygous deletion of the CT gene eliminated CT but did not affect maternal or fetal ionized calcium levels, the rate of fetal-placental calcium transfer, serum phosphorus levels, or the amount of mineral present in each fetal skeleton. It also did not affect the gross skeletal morphology, the expression of important bone markers, fetal serum parathyroid hormone (PTH) levels, or calbindin-D₉K or Ca⁺⁺ ATPase expression in placental tissue. However, maternal loss of CT resulted in a reduction in litter size while both maternal and fetal loss of CT resulted in a reduction in the concentration of magnesium in the fetal circulation and possibly in the fetal skeleton. Our studies also confirm that the genes for CT and the CT-receptor are located in the murine placenta. -- In summary, these results suggest that CT cannot cross the placenta, that the maternal absence of CT reduces the total number of fetuses that survive at term, and that CT may selectively regulate aspects of magnesium metabolism in the fetus. However, it appears that the complete loss of either maternal or fetal CT does not perturb the other measured parameters of fetal-placental calcium homeostasis.