title: Pattern of secretion of pregnancy-associated plasma protein-A (PAPP-A) during pregnancies complicated by fetal aneuploidy, in vivo and in vitro.
abstract: BACKGROUND
  Pregnancy-associated placental protein-A (PAPP-A) is a metalloprotease which circulates as an hetero-tetramer in maternal blood. Its maternal serum concentration in fetal trisomy 21 is decreased during the first trimester, so that PAPP-A is a useful screening biomarker. However, the regulation of PAPP-A placental secretion is unclear. We therefore investigated the secretion of PAPP-A in pregnancies complicated by fetal aneuploidies, both in vivo and in vitro.
  
  
  METHODS
  Maternal serum collected between 10 WG and 33 WG during 7014 normal pregnancies and 96 pregnancies complicated by fetal trisomy 21, 18, and 13 were assayed for PAPP-A using the Immulite 2000xpi system®. The pregnancies were monitored using ultrasound scanning, fetal karyotyping and placental analysis. Villous cytotrophoblasts were isolated from normal and trisomic placenta and cultured to investigate PAPP-A secretion in vitro (n=6).
  
  
  RESULTS
  An increased nuchal translucency during the first trimester is a common feature of many chromosomal defect but each aneuploidy has its own syndromic pattern of abnormalities detectable at the prenatal ultrasound scanning and confirmed at the fetal examination thereafter. PAPP-A levels rise throughout normal pregnancy whereas in trisomy 21, PAPP-A levels were significantly decreased, but only during the first trimester. PAPP-A levels were decreased in trisomy 13 and sharply in trisomy 18, whatever the gestational age. In vitro, PAPP-A secretion was decreased in aneuploidy, and associated with decreased hCG secretion in Trisomy 21 and 18. These biochemical profiles did not appear to be linked to any specific histological lesions affecting the placenta.
  
  
  CONCLUSIONS
  These profiles may reflect different quantitative and qualitative placental dysfunctions in the context of these aneuploidies.
authors.forename: Marie Clémence
authors.initials: MC
authors.lastname: Leguy
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brun
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pidoux
authors.forename: Houria
authors.initials: H
authors.lastname: Salhi
authors.forename: Agnes
authors.initials: A
authors.lastname: Choiset
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Menet
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
authors.forename: Vassilis
authors.initials: V
authors.lastname: Tsatsaris
authors.affiliation: Hormonology CHU Cochin AP-HP, 27 rue du Fbg St Jacques, Paris, France. jean.guibourdenche@cch.aphp.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Guibourdenche
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000097:blood / Q000378:metabolism; D025063:Chromosome Disorders / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D015331:Cohort Studies; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005865:Gestational Age; D006801:Humans; D048208:Nuchal Translucency Measurement / Q000379:methods; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics*; D000073839:Trisomy 13 Syndrome; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human