Role of calcitriol in regulating fetal mineral homeostasis and bone development

Alhani, Kamal (2019) Role of calcitriol in regulating fetal mineral homeostasis and bone development. Masters thesis, Memorial University of Newfoundland.

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Abstract

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.

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