Calcitriol has a critical role in regulating mineral and bone metabolism in children and adults.
However, its role in fetal mineral and bone metabolism is not yet well understood. Hence, we
investigated the role of calcitriol during fetal development using a knockout mouse model
involving ablation of the Cyp27b1 gene encoding 1α-hydroxylase that converts 25-
hydroxyvitamin D₃ to 1,25-dihydroxyvitamin D₃ (calcitriol). Specifically, this study compared
Cyp27b1 null fetuses to wild type (WT) fetuses from heterozygous (Cyp27b1⁺/⁻) mothers. Our
findings showed that Cyp27b1 null fetuses had normal calcium and phosphorus levels in serum
and amniotic fluid, normal placental mineral transport, as well as normal skeletal ash weight,
mineral content and bone morphology. The quantitative RT-PCR confirmed the loss of Cyp27b1
expression in null fetal kidneys, but there were no changes in fetal renal or placental expression
of calciotropic and phosphotropic genes. Although the calcitriol level in Cyp27b1 null fetuses
was significantly lower than the WT siblings, it was not undetectable, likely due to placental
transfer of maternal calcitriol to the fetuses. To investigate this possibility, a preliminary study
was conducted to assess the fetal mineral and bone metablism of Cyp27b1 null fetuses born from
Cyp27b1 null mothers. Pilot data showed that these fetuses had normal serum calcium and
skeletal ash weight and morphology. In summary, our findings herein suggest that calcitriol may
not play a role in fetal mineral and bone metabolism. However, further studies involving
Cyp27b1 null fetuses from null mothers are required to conclusively support this conclusion
