title: Pre-eclampsia and expression of heparin-binding EGF-like growth factor.
abstract: BACKGROUND
  Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women.
  
  
  METHODS
  We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia.
  
  
  RESULTS
  HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF.
  
  
  CONCLUSIONS
  In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension.
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201-1415, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Leach
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Brian
authors.initials: B
authors.lastname: Kilburn
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
authors.forename: Anthony
authors.initials: A
authors.lastname: Johnson
authors.forename: Faisal
authors.initials: F
authors.lastname: Qureshi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jacques
authors.forename: D Randall
authors.initials: DR
authors.lastname: Armant
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000235:genetics; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007231:Infant, Newborn; D007234:Infant, Premature; D036341:Intercellular Signaling Peptides and Proteins; D010920:Placenta / Q000737:chemistry* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000032:analysis; D017978:Receptors, Growth Factor; D018709:Statistics, Nonparametric; D014327:Trophoblasts / Q000737:chemistry / Q000473:pathology
chemical_list: C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D004815:Epidermal Growth Factor