title: The effect of gestational age on angiogenic gene expression in the rat placenta.
abstract: The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes during gestation as the fetus develops and as demands for energy substrate transfer and gas exchange increase. The molecular mechanisms that coordinate these changes have yet to be fully elucidated. The study performed a large scale screen of the transcriptome of the rat placenta throughout mid-late gestation (E14.25-E20) with emphasis on characterizing gestational age associated changes in the expression of genes involved in angiogenic pathways. Sprague Dawley dams were sacrificed at E14.25, E15.25, E17.25 and E20 (n = 6 per group) and RNA was isolated from one placenta per dam. Changes in placental gene expression were identified using Illumina Rat Ref-12 Expression BeadChip Microarrays. Differentially expressed genes (>2-fold change, <1% false discovery rate, FDR) were functionally categorised by gene ontology pathway analysis. A subset of differentially expressed genes identified by microarrays were confirmed using Real-Time qPCR. The expression of thirty one genes involved in the angiogenic pathway was shown to change over time, using microarray analysis (22 genes displayed increased and 9 gene decreased expression). Five genes (4 up regulated: Cd36, Mmp14, Rhob and Angpt4 and 1 down regulated: Foxm1) involved in angiogenesis and blood vessel morphogenesis were subjected to further validation. qPCR confirmed late gestational increased expression of Cd36, Mmp14, Rhob and Angpt4 and a decrease in expression of Foxm1 before labour onset (P<0.0001). The observed acute, pre-labour changes in the expression of the 31 genes during gestation warrant further investigation to elucidate their role in pregnancy.
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Vaswani
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Melissa Wen-Ching
authors.initials: MW
authors.lastname: Hum
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Hsiu-Wen
authors.initials: HW
authors.lastname: Chan
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ryan
authors.affiliation: School of Medicine (Optometry), Deakin University, Waurn Ponds, Victoria, Australia ; Department of Anatomy & Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Wood-Bradley
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Marloes Dekker
authors.initials: MD
authors.lastname: Nitert
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.affiliation: School of Medicine (Optometry), Deakin University, Waurn Ponds, Victoria, Australia ; Department of Anatomy & Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Herston, Queensland, Australia.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018919:Neovascularization, Physiologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger