Document Detail


Characterization of an animal model of pregnancy-induced vitamin D deficiency due to metabolic gene dysregulation.
MedLine Citation:
PMID:  24326417     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Objective: 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. Approach and Results: 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 pre-pregnancy, pregnancy, and postpartum. Analysis of the active metabolite, 1,25-(OH)2-D, showed a 2-fold increase in pregnant SD and LW rats, but a near 10-fold decrease in pregnant BN rats compared to non-pregnant 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 single-nucleotide polymorphisms. Lastly, supplementation with 1,25-(OH)2-D significantly improved the reproductive phenotype of BN rats by increasing litter size, and maternal-fetal weight outcomes. Conclusions: We conclude that BN rats represent a novel animal model of pregnancy-specific vitamin D deficiency linked to pregnancy complications. Vitamin D deficiency in BN rats correlates with maternal renal CYP24a1 upregulation followed by CYP27b1 upregulation.
Authors:
Ravi Goyal; Lubo Zhang; Arlin B Blood; David J Baylink; Lawrence D Longo; Bryan Oshiro; Eugenia Mata-Greenwood
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-10
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Loma Linda University, School of Medicine.
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