title: Homeobox gene Distal-less 3 is a regulator of villous cytotrophoblast differentiation and its expression is increased in human idiopathic foetal growth restriction.
abstract: Human idiopathic foetal growth restriction (FGR) is frequently associated with placental insufficiency. In our previous studies, we have reported the isolation and characterisation of the homeobox gene Distal-less 3 (DLX3) in the human placenta. In this study, we have investigated the level of DLX3 expression in idiopathic FGR-affected placentae and determined its functional role in villous trophoblast differentiation. FGR-affected placentae (n = 25) were collected based on well-defined clinical criteria and matched for gestation with control uncomplicated pregnancies (n = 25). Real-time polymerase chain reaction and immunoblotting showed increased DLX3 mRNA and protein expression in FGR-affected placentae compared with gestation-matched controls. Qualitative immunohistochemistry revealed DLX3 localisation in the syncytiotrophoblast, cytotrophoblasts and endothelial cells surrounding the foetal capillaries in both FGR-affected and control placentae. Down-regulation of DLX3 in primary villous trophoblast cells and a trophoblast-derived cell line showed decreased expression of differentiation markers, 3βHSD, βhCG and syncytin. Therefore, we conclude that increased DLX3 expression in FGR may contribute to trophoblast dysfunction observed in FGR.
authors: Department of Perinatal Medicine, Pregnancy Research Centre, Royal Women's Hospital, Parkville, VIC 3052, Australia.
authors: Amy
authors: A
authors: Chui
authors: Charmaine
authors: C
authors: Tay
authors: Melanie
authors: M
authors: Cocquebert
authors: Penelope
authors: P
authors: Sheehan
authors: Niroshani A
authors: NA
authors: Pathirage
authors: Susan
authors: S
authors: Donath
authors: Thierry
authors: T
authors: Fournier
authors: Josette
authors: J
authors: Badet
authors: Daniele
authors: D
authors: Evain-Brion
authors: Shaun P
authors: SP
authors: Brennecke
authors: Bill
authors: B
authors: Kalionis
authors: Padma
authors: P
authors: Murthi
mesh_terms: D016022:Case-Control Studies; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000378:metabolism; D010927:Placental Insufficiency / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology*; D015854:Up-Regulation
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors