PMID- 26121239
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 6
DP  - 2015
TI  - Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on 
      Placental Morphology, Function and Pregnancy Outcome.
PG  - e0131287
LID - 10.1371/journal.pone.0131287 [doi]
LID - e0131287
AB  - 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.
FAU - Wilson, Rebecca L
AU  - Wilson RL
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - Buckberry, Sam
AU  - Buckberry S
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - Spronk, Fleur
AU  - Spronk F
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - Laurence, Jessica A
AU  - Laurence JA
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - Leemaqz, Shalem
AU  - Leemaqz S
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - O'Leary, Sean
AU  - O'Leary S
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
FAU - Bianco-Miotto, Tina
AU  - Bianco-Miotto T
AD  - Robinson Research Institute, Adelaide, Australia; School of Agriculture, Food and 
      Wine, University of Adelaide, Adelaide, Australia.
FAU - Du, Jing
AU  - Du J
AD  - Robinson Research Institute, Adelaide, Australia; Shanghai Institute of Planned 
      Parenthood Research, Shanghai, China.
FAU - Anderson, Paul H
AU  - Anderson PH
AD  - School of Pharmacy and Medical Sciences, Division of Health Sciences, University 
      of South Australia, Adelaide, Australia.
FAU - Roberts, Claire T
AU  - Roberts CT
AD  - Robinson Research Institute, Adelaide, Australia; School of Paediatrics and 
      Reproductive Health, University of Adelaide, Adelaide, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150629
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (deptor protein, mouse)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetus/*metabolism
MH  - *Gene Deletion
MH  - Gene Expression Profiling
MH  - Genotype
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Oligonucleotide Array Sequence Analysis
MH  - Placenta/*anatomy & histology/metabolism/*physiology
MH  - Pregnancy
MH  - Pregnancy Outcome/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Calcitriol/*genetics
MH  - Reproducibility of Results
MH  - Transcriptome/genetics
MH  - Vitamin D3 24-Hydroxylase/genetics
PMC - PMC4488298
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/06/30 06:00
MHDA- 2016/04/06 06:00
PMCR- 2015/06/29
CRDT- 2015/06/30 06:00
PHST- 2015/05/18 00:00 [received]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/06/30 06:00 [entrez]
PHST- 2015/06/30 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
PHST- 2015/06/29 00:00 [pmc-release]
AID - PONE-D-15-21468 [pii]
AID - 10.1371/journal.pone.0131287 [doi]
PST - epublish
SO  - PLoS One. 2015 Jun 29;10(6):e0131287. doi: 10.1371/journal.pone.0131287. 
      eCollection 2015.