Downstream targets of the homeobox gene DLX3 are differentially expressed in the placentae of pregnancies affected by human idiopathic fetal growth restriction
Copyright policy )Downstream targets of the homeobox gene DLX3 are differentially expressed in the placentae of pregnancies affected by human idiopathic fetal growth restriction
Human idiopathic fetal growth restriction (FGR) is associated with placental insufficiency. Previously, we reported that the expression of homeobox gene Distal-less 3 (DLX3) is increased in idiopathic FGR placentae and is a regulator of villous trophoblast differentiation. Here, we identify the downstream targets of DLX3 in trophoblast-derived cell lines. We modelled the high levels of DLX3 in FGR using an over-expression plasmid construct and complemented this using short-interference RNA (siRNA) for inactivation in cultured cells. Using a real-time PCR-based gene profiling, candidate target genes of DLX3 over-expression and inactivation were identified as regulators of trophoblast differentiation; GATA2 and PPARγ. The expression of GATA2 and PPARγ were further assessed in placental tissues and showed increased mRNA and protein levels in FGR-affected tissues compared with gestation-matched controls. We conclude that DLX3 orchestrates the expression of multiple regulators of trophoblast differentiation and that expression of these regulatory genes is abnormal in FGR.
- University of Paris France
- UNIVERSITE PARIS DESCARTES France
- French Institute of Health and Medical Research France
- University of Melbourne Australia
- King Saud bin Abdulaziz University for Health Sciences Saudi Arabia
Adult, Placenta, 610, Fetal growth, Homeobox genes, Cell Line, 618, Pregnancy, Humans, RNA, Messenger, RNA, Small Interfering, Genetic Association Studies, Homeodomain Proteins, Fetal Growth Retardation, Gene Expression Profiling, Trophoblast, Reproducibility of Results, Trophoblasts, GATA2 Transcription Factor, PPAR gamma, Gene Expression Regulation, Human placenta, Female, Plasmids, Signal Transduction, Transcription Factors
Adult, Placenta, 610, Fetal growth, Homeobox genes, Cell Line, 618, Pregnancy, Humans, RNA, Messenger, RNA, Small Interfering, Genetic Association Studies, Homeodomain Proteins, Fetal Growth Retardation, Gene Expression Profiling, Trophoblast, Reproducibility of Results, Trophoblasts, GATA2 Transcription Factor, PPAR gamma, Gene Expression Regulation, Human placenta, Female, Plasmids, Signal Transduction, Transcription Factors
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