title: Downstream targets of the homeobox gene DLX3 are differentially expressed in the placentae of pregnancies affected by human idiopathic fetal growth restriction.
abstract: 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.
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre, Royal Women's Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Chui
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abumaree
authors.forename: Melanie
authors.initials: M
authors.lastname: Cocquebert
authors.forename: Thierry
authors.initials: T
authors.lastname: Fournier
authors.forename: Daniele
authors.initials: D
authors.lastname: Evain-Brion
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D010957:Plasmids / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C088334:Distal-less homeobox proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D018398:Homeodomain Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors
keywords: Fetal growth; Homeobox genes; Human placenta; Trophoblast