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Type: Journal article
Title: Vitamin D receptor gene ablation in the conceptus has limited effects on placental morphology, function and pregnancy outcome
Author: Wilson, R.
Buckberry, S.
Spronk, F.
Laurence, J.
Leemaqz, S.
O'Leary, S.
Bianco-Miotto, T.
Du, J.
Anderson, P.
Roberts, C.
Citation: PLoS One, 2015; 10(6):e0131287-1-e0131287-17
Publisher: Public Library of Science
Issue Date: 2015
ISSN: 1932-6203
Statement of
Rebecca L. Wilson, Sam Buckberry, Fleur Spronk, Jessica A. Laurence, Shalem Leemaqz, Sean O, Leary, Tina Bianco-Miotto, Jing Du, Paul H. Anderson, Claire T. Roberts
Abstract: Vitamin D deficiency has been implicated in the pathogenesis of several pregnancy complications attributed to impaired or abnormal placental function, but there are few clues indicating the mechanistic role of vitamin D in their pathogenesis. To further understand the role of vitamin D receptor (VDR)-mediated activity in placental function, we used heterozygous Vdr ablated C57Bl6 mice to assess fetal growth, morphological parameters and global gene expression in Vdr null placentae. Twelve Vdr+/- dams were mated at 10-12 weeks of age with Vdr+/- males. At day 18.5 of the 19.5 day gestation in our colony, females were euthanised and placental and fetal samples were collected, weighed and subsequently genotyped as either Vdr+/+, Vdr+/- or Vdr-/-. Morphological assessment of placentae using immunohistochemistry was performed and RNA was extracted and subject to microarray analysis. This revealed 25 genes that were significantly differentially expressed between Vdr+/+ and Vdr-/- placentae. The greatest difference was a 6.47-fold change in expression of Cyp24a1 which was significantly lower in the Vdr-/- placentae (P<0.01). Other differentially expressed genes in Vdr-/- placentae included those involved in RNA modification (Snord123), autophagy (Atg4b), cytoskeletal modification (Shroom4), cell signalling (Plscr1, Pex5) and mammalian target of rapamycin (mTOR) signalling (Deptor and Prr5). Interrogation of the upstream sequence of differentially expressed genes identified that many contain putative vitamin D receptor elements (VDREs). Despite the gene expression differences, this did not contribute to any differences in overall placental morphology, nor was function affected as there was no difference in fetal growth as determined by fetal weight near term. Given our dams still expressed a functional VDR gene, our results suggest that cross-talk between the maternal decidua and the placenta, as well as maternal vitamin D status, may be more important in determining pregnancy outcome than conceptus expression of VDR.
Keywords: Fetus; Placenta; Animals; Mice, Inbred C57BL; Intracellular Signaling Peptides and Proteins; Receptors, Calcitriol; Pregnancy Outcome; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Gene Expression Profiling; Gene Deletion; Pregnancy; Genotype; Female; Male; Real-Time Polymerase Chain Reaction; Transcriptome; Vitamin D3 24-Hydroxylase
Rights: © 2015 Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030031058
DOI: 10.1371/journal.pone.0131287
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