title: Homeobox gene HLX1 expression is decreased in idiopathic human fetal growth restriction.
abstract: Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Identifiable causes of FGR account for approximately 30% of cases, but the remainder are idiopathic and are frequently associated with placental malfunction. Previously, we isolated the homeobox gene HLX1 and provided evidence for a regulatory role in normal placental development. Here, we investigated whether placental HLX1 expression levels are changed in placentas from idiopathic FGR pregnancies. Real-time polymerase chain reaction quantitation showed reduced HLX1 mRNA levels with advancing gestation age (preterm control placentas, 27 to 35 weeks, 1.1 +/- 0.3, n = 13, versus term placentas 36 to 41 weeks, 0.74 +/- 0.02, n = 12, P < 0.005). FGR-affected placentas had significantly lower levels of HLX1 expression compared with gestation age-matched controls (0.36 +/- 0.07 versus 1.05 +/- 0.2, n = 25, P < 0.001). Immunoblotting with a rabbit polyclonal HLX1 antibody revealed reduced levels of HLX1 in FGR-affected placentas compared with controls (481.07 +/- 12.3 versus 2766.7 +/- 30.3, n = 10, P < 0.001). Immunohistochemistry showed a qualitative decrease in HLX1 immunoreactivity in FGR-affected term placentas compared with controls. This is the first demonstration that a homeobox transcriptional regulator shows altered expression in an important human placental disorder, suggesting that decreased HLX1 levels contribute to the abnormalities in placental developmental seen in idiopathic FGR.
authors.affiliation: Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, 132 Grattan St., Carlton, Victoria 3053, Australia.
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
authors.forename: Vicki
authors.initials: V
authors.lastname: Doherty
authors.forename: Joanne
authors.initials: J
authors.lastname: Said
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C084058:HLX protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors