title: Homeobox gene transforming growth factor β-induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction.
abstract: Abnormal trophoblast function is associated with human fetal growth restriction (FGR). Targeted disruption of homeobox gene transforming growth β-induced factor (TGIF-1) results in placental dysfunction in the mouse. The role of human TGIF-1 in placental cell function is unknown. The aims of this study were to determine the expression of TGIF-1 in human idiopathic FGR-affected placentae compared with gestation-matched controls (GMC), to elucidate the functional role of TGIF-1 in trophoblasts and to identify its downstream targets. Real-time PCR and immunoblotting revealed that TGIF-1 mRNA and protein expression was significantly increased in FGR-affected placentae compared with GMC (n = 25 in each group P < 0.05). Immunoreactive TGIF-1 was localized to the villous cytotrophoblasts, syncytiotrophoblast, microvascular endothelial cells and in scattered stromal cells in both FGR and GMC. TGIF-1 inactivation in BeWo cells using two independent siRNA resulted in significantly decreased mRNA and protein of trophoblast differentiation markers, human chorionic gonadotrophin (CGB/hCG), syncytin and 3β-hydroxysteroid dehydrogenase/3β-honest significant difference expression. Our data demonstrate that homeobox gene TGIF-1 is a potential up-stream regulator of trophoblast differentiation and the altered TGIF-1 expression may contribute to aberrant villous trophoblast differentiation in FGR.
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre, and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Parkville, VIC 3052, Australia.
authors.forename: Niroshani A
authors.initials: NA
authors.lastname: Pathirage
authors.forename: Melanie
authors.initials: M
authors.lastname: Cocquebert
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abumaree
authors.forename: Ursula
authors.initials: U
authors.lastname: Manuelpillai
authors.forename: Anthony
authors.initials: A
authors.lastname: Borg
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Keogh
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.forename: Daniele
authors.initials: D
authors.lastname: Evain-Brion
authors.forename: Thierry
authors.initials: T
authors.lastname: Fournier
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D015686:Gene Products, env; D018398:Homeodomain Proteins; D011257:Pregnancy Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human; C405335:syncytin; D015096:3-Hydroxysteroid Dehydrogenases
keywords: fetal growth restriction; gene expression; homeobox genes; placenta; pregnancy