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We used the calcitonin/calcitonin gene-related peptide (CGRP)-alpha gene knockout model (Ct/Cgrp null) to determine whether calcitonin and CGRPalpha are required for normal fetal mineral homeostasis and placental calcium transfer. Heterozygous (Ct/Cgrp(+/-)) and Ct/Cgrp null females were mated to Ct/Cgrp(+/-) males. One or two days before term, blood was collected from mothers and fetuses and analyzed for ionized Ca, Mg, P, parathyroid hormone (PTH), and calcitonin. Amniotic fluid was collected for Ca, Mg, and P. To quantify skeletal mineral content, fetuses were reduced to ash, dissolved in nitric acid, and analyzed by atomic absorption spectroscopy for total Ca and Mg. Placental transfer of (45)Ca at 5 min was assessed. Ct/Cgrp null mothers had significantly fewer viable fetuses in utero compared with Ct/Cgrp(+/-) and wild-type mothers. Fetal serum Ca, P, and PTH did not differ by genotype, but serum Mg was significantly reduced in null fetuses. Placental transfer of (45)Ca at 5 min was normal. The calcium content of the fetal skeleton was normal; however, total Mg content was reduced in Ct/Cgrp null skeletons obtained from Ct/Cgrp null mothers. In summary, maternal absence of calcitonin and CGRPalpha reduced the number of viable fetuses. Fetal absence of calcitonin and CGRPalpha selectively reduced serum and skeletal magnesium content but did not alter ionized calcium, placental calcium transfer, and skeletal calcium content. These findings indicate that calcitonin and CGRPalpha are not needed for normal fetal calcium metabolism but may regulate aspects of fetal Mg metabolism.

We utilized a vitamin D receptor (VDR) gene knockout model to study the effects of maternal and fetal absence of VDR on maternal fertility, fetal-placental calcium transfer, and fetal mineral homoeostasis. Vdr null mice were profoundly hypocalcemic, conceived infrequently, and had significantly fewer viable fetuses in utero that were also of lower body weight. Supplementation of a calcium-enriched diet increased the rate of conception in Vdr nulls but did not normalize the number or weight of viable fetuses. Among offspring of heterozygous (Vdr+/-) mothers (wild type, Vdr+/-, and Vdr null fetuses), there was no alteration in serum Ca, P, or Mg, parathyroid hormone, placental 45Ca transfer, Ca and Mg content of the fetal skeleton, and morphology and gene expression in the fetal growth plates. Vdr null fetuses did have threefold increased 1,25-dihydroxyvitamin D levels accompanied by increased 1α-hydroxylase mRNA in kidney but not placenta; a small increase was also noted in placental expression of parathyroid hormone-related protein (PTHrP). Among offspring of Vdr null mothers, Vdr+/- and Vdr null fetuses had normal ionized calcium levels and a skeletal ash weight that was appropriate to the lower body weight. Thus our findings indicate that VDR is not required by fetal mice to regulate placental calcium transfer, circulating mineral levels, and skeletal mineralization. Absence of maternal VDR has global effects on fetal growth that were partly dependent on maternal calcium intake, but absence of maternal VDR did not specifically affect fetal mineral homeostasis. [ABSTRACT FROM AUTHOR]

Abstract: Neural tube defects are congenital abnormalities caused by failure of the neural tube to close during embryogenesis. We investigated trace elements (zinc, copper, manganese, cobalt, nickel, molybdenum, cadmium), livers, pancreata, sciatic nerves, diaphragms, and kidneys collected at autopsy from 33 anencephalic fetuses and 22 control fetuses. Collections were done on the right side using a titanium scalpel, plastic forceps, and acid-washed materials. Samples were wet ashed and analyzed using inductively coupled plasma mass spectrometry. The gestational age and birth weight (mean ± SD) of anencephalic fetuses were 25.8 ± 8 weeks and 729 ± 879 g, respectively; those of control fetuses, 28 ± 8 weeks and 1340 ± 1216 g, respectively. Liver concentrations (ppm, dry weight, mean ± SEM) of Zn (1075 ± 56 vs 668 ± 75; P = .001) increased in anencephalic fetuses, suggesting defective transport of Zn. Whether this is part of the cause of neural tube defects or a result of the disease is unclear. [Copyright &y& Elsevier]