The role of calcitriol in regulating fetal bone and mineral metabolism, as elucidated through study of Cyp28b1 null fetal mice

Ryan, Brittany (2019) The role of calcitriol in regulating fetal bone and mineral metabolism, as elucidated through study of Cyp28b1 null fetal mice. Masters thesis, Memorial University of Newfoundland.

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Abstract

Does calcitriol play any role in regulating mineral metabolism or skeletal development in utero? Studies of Boston and Leuven vitamin D receptor (VDR) ablation models reported that Vdr null fetuses have normal serum minerals, parathyroid hormone (PTH), skeletal morphology and mineralization. However, Vdr null fetuses also have increased serum calcitriol, placental calcium transport, and placental expression of Pthrp and Trpv6. In the present study, we examined Cyp27b1 null fetal mice, which do not make calcitriol, to determine if loss of calcitriol has the same consequences as loss of VDR. Cyp27b1 null and WT females were mated to Cyp27b1⁺/⁻ males, which generated Cyp27b1 null and Cyp27b1⁺/⁻ fetuses from Cyp27b1 null mothers, and Cyp27b1⁺/⁻ and WT fetuses from WT mothers. We confirmed that calcitriol was undetectable in Cyp27b1 null fetuses; therefore, they truly lacked calcitriol and were a useful model to address the research question. Cyp27b1 null fetuses had normal serum calcium, serum phosphorus, PTH, skeletal ash weight, ash mineral content, tibial length and morphology. Placental calcium transport was normal in Cyp27b1 null fetuses, while qPCR of placental mRNA confirmed loss of Cyp27b1 expression but no change in expression of key genes involved in placental mineral transport, including transient receptor potential cation channel subfamily V member 6 (Trpv6) and parathyroid hormone related protein (Pthrp). In summary, loss of calcitriol in Cyp27b1 null fetuses borne of Cyp27b1 null mothers did not significantly alter any measured parameter of mineral or bone homeostasis.

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