Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation

Ravi Goyal, Lubo Zhang, Arlin B. Blood, David J. Baylink, Lawrence D. Longo, Bryan Oshiro, Eugenia Mata-Greenwood

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Vitamin D deficiency has been associated with pregnancy complications such as preeclampsia, gestational diabetes, and recurrent miscarriage. Therefore, we hypothesized differences in vitamin D status between healthy [Sprague-Dawley (SD) and Lewis (LW)] and complicated [Brown Norway (BN)] rat pregnancies. In SD, LW, and BN rats, we analyzed the maternal plasma levels of the vitamin D metabolites 25-OH-D and 1,25-(OH)2-D at prepregnancy, pregnancy, and postpartum. Analysis of the active metabolite 1,25-(OH)2-D showed a twofold increase in pregnant SD and LW rats but a nearly 10-fold decrease in pregnant BN rats compared with nonpregnant controls. BN rats had a pregnancy-dependent upregulation of CYP24a1 expression, a key enzyme that inactivates vitamin D metabolites. In contrast, the maternal renal expression of CYP24a1 in SD and LW rats remained constant throughout pregnancy. Analysis of the vitamin D receptor (VDR) indicated that LW and SD but not BN rats experience a pregnancy-induced 10-fold decrease in maternal renal VDR protein levels. Further analysis of bisulfite-converted and genomic DNA indicated that the observed differences in maternal renal regulation of CYP24a1 during pregnancy and lactation are not due to differences in CYP24a1 promoter methylation or singlenucleotide polymorphisms. Finally, supplementation with 1,25- (OH)2-D significantly improved the reproductive phenotype of BN rats by increasing litter size and maternal-fetal weight outcomes. We conclude that BN rats represent a novel animal model of pregnancyspecific vitamin D deficiency that is linked to pregnancy complications. Vitamin D deficiency in BN rats correlates with maternal renal CYP24a1 upregulation followed by CYP27b1 upregulation.

Original languageEnglish (US)
Pages (from-to)E256-E266
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number3
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • CYP24a1
  • Calcitriol
  • Kidney
  • Metabolism
  • Placenta

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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