Fetal parathyroids are not required to maintain placental calcium transport

We used Hoxa3 knockout mice and other mouse models to study the role of the fetal parathyroids in fetal calcium homeostasis. Hoxa3-null fetuses lack p arathyroid glands, and absence of parathyroid hormone (PTH) was confirmed w ith a rodent PTH immunoradiometric assay. The ionized calcium level of Hoxa 3-null fetuses was significantly lower than that of wild-type or heterozygo us littermates or of the mother. Both the rate of placental calcium transfe r and the plasma PTHrP level were normal in Hoxa3 mutants and their heteroz ygous siblings. Because we had previously observed an increase in placental calcium transfer in PTH/PTHrP receptor I-null (Pthr1-null) fetuses, we ass ayed plasma PTHrP in those mice. Prhr1-null fetuses had plasma PTHrP levels 11-fold higher than those of their littermates. Northern analysis, immunoh istochemical, and in situ hybridization studies of Pthr1-null fetuses indic ated that liver and placenta had increased expression of PTHrP. In summary, loss of fetal parathyroids in Hoxa3-null fetuses caused marked hypocalcemi a but did not alter placental calcium transfer or the circulating PTHrP lev el. The findings in the Pthr1-null fetuses indicate that several tissues ma y contribute to the circulating PTHrP level in fetal mice.