title: Differential expression of human placental PAPP-A2 over gestation and in preeclampsia.
abstract: BACKGROUND
  Pregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia.
  
  
  METHODS
  Placental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera.
  
  
  RESULTS
  PAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood.
  
  
  CONCLUSIONS
  PAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation.
authors.affiliation: University of Colorado School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Aurora, CO, USA. Electronic address: Anita.Kramer@ucdenver.edu.
authors.forename: Anita W
authors.initials: AW
authors.lastname: Kramer
authors.affiliation: University of Colorado School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Aurora, CO, USA. Electronic address: llamalesmith@ucsd.edu.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Lamale-Smith
authors.affiliation: University of Colorado School of Medicine, Department of Obstetrics and Gynecology, 12631 E. 17th Avenue, Aurora, CO, USA. Electronic address: vwinn@stanford.edu.
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Winn
mesh_terms: D016022:Case-Control Studies; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000235:genetics / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000235:genetics / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A
keywords: PAPP-A2; Placenta; Preeclampsia