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Published on: April 14, 2023
The effect of Vdr gene ablation on global gene expression in the mouse placenta
Sam Buckberry1, Fleur Spronk1, Rebecca L Wilson1
1Robinson Research Institute, The University of Adelaide, School of Paediatrics and Reproductive Health, Adelaide, Australia.
Abstract:
The effects of vitamin D are mediated through the vitamin D receptor (VDR), a predominantly nuclear receptor, expressed in numerous tissues including the placenta. VDR and the retinoid X receptor (RXR) form a dimer complex which binds to genomic vitamin D responsive elements located primarily in promoter regions and recruit cell-specific transcription factor complexes which regulate the expression of numerous genes. To investigate the role of VDR on regulating placental gene expression, mice heterozygous (+/-) for an ablated Vdr allele (C57Bl6 strain B6.129S4-VDRtm1Mbd/J, Jackson Laboratory) were mated to generate Vdr(+/+), Vdr(+/-) and Vdr (-/-) fetuses and placental samples were collected at day 18.5 of pregnancy. RNA was isolated from placental tissue with global gene expression measured using Affymetrix Mouse Gene 2.1 ST Arrays to assess the effects of VDR on global gene expression in the placenta. All raw array data are deposited in Gene Expression Omnibus (GEO) under accession GSE61583.
Insights
Vitamin D receptor (VDR) plays a crucial role in placental gene expression. Ablating VDR in mice significantly altered global gene expression patterns in placental tissue, highlighting its importance in pregnancy.
Area of Science:
- Endocrinology
- Genomics
- Developmental Biology
Background:
- The vitamin D receptor (VDR) mediates vitamin D's effects, acting as a nuclear receptor crucial for gene regulation.
- VDR forms a heterodimer with the retinoid X receptor (RXR), binding to DNA to influence gene transcription.
Purpose of the Study:
- To investigate the role of VDR in regulating placental gene expression.
- To assess the impact of VDR ablation on global gene expression in mouse placenta.
Main Methods:
- Mice with ablated Vdr alleles (Vdr -/-) were generated alongside wild-type (Vdr +/+) and heterozygous (Vdr +/-) controls.
- Placental tissues were collected at day 18.5 of gestation.
- Global gene expression was analyzed using Affymetrix Mouse Gene 2.1 ST Arrays.
Main Results:
- VDR ablation led to significant alterations in global gene expression within the placenta.
- Specific gene expression profiles were identified in Vdr (-/-) placentas compared to controls.
- Data deposited in Gene Expression Omnibus (GEO) under accession GSE61583.
Conclusions:
- VDR is a key regulator of placental gene expression.
- The absence of VDR profoundly impacts the placental transcriptome.
- Findings underscore the importance of VDR signaling in placental development and function.
