title: Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction.
abstract: BACKGROUND
  Fetal growth restriction (FGR) is a leading cause of perinatal mortality, yet no reliable screening test exists. Placental specific mRNA in the maternal circulation may reflect changes in the placental transcriptome in FGR and could be a novel biomarker for FGR.
  
  
  OBJECTIVE
  The aim of the study was to identify placental specific RNA detectable in the maternal circulation and examine whether they are differentially expressed in severe preterm FGR.
  
  
  METHODS
  In silico screening was used to identify placental specific RNAs. Their expression in cases of severe FGR vs controls was examined in both maternal blood and placenta by microarray, RT-PCR, and in situ hybridization.
  
  
  RESULTS
  Via in silico analysis, we identified 137 genes very highly expressed in the placenta relative to other tissues. Using microarray, we found that they were detectable in the maternal blood and were globally dysregulated with preterm FGR; 75 genes (55%) had a ≥1.5-fold differential expression compared to controls. Eight genes (ERVWE-1, PSG1, PLAC4, TAC3, PLAC3, CRH, CSH1, and KISS1) were validated by RT-PCR to be significantly increased in both maternal blood and placenta in a larger cohort of severe FGR compared to controls. In situ hybridization confirmed PAPPA2 and ERVWE-1 localized to the syncytiotrophoblast.
  
  
  CONCLUSIONS
  There is global differential expression of placental specific mRNA in the maternal blood in pregnancies complicated by severe preterm FGR. Placental specific mRNA in maternal blood may represent a new class of biomarkers for preterm FGR.
authors: Department of Obstetrics and Gynecology, University of Melbourne, Mercy Hospital for Women, 163 Studley Road, Heidelberg 3084, Victoria, Australia.
authors: Clare L
authors: CL
authors: Whitehead
authors: Susan P
authors: SP
authors: Walker
authors: Louie
authors: L
authors: Ye
authors: Sonali
authors: S
authors: Mendis
authors: Tu'uhevaha J
authors: TJ
authors: Kaitu'u-Lino
authors: Martha
authors: M
authors: Lappas
authors: Stephen
authors: S
authors: Tong
mesh_terms: D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism; D015686:Gene Products, env / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood; D059648:Kisspeptins / Q000235:genetics; D010920:Placenta / Q000502:physiology*; D010928:Placental Lactogen / Q000235:genetics; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D018039:Receptors, Tachykinin / Q000235:genetics; D059467:Transcriptome
chemical_list: D015686:Gene Products, env; C106628:KISS1 protein, human; D059648:Kisspeptins; D011257:Pregnancy Proteins; D011268:Pregnancy-Specific beta 1-Glycoproteins; D012333:RNA, Messenger; D018039:Receptors, Tachykinin; C405335:syncytin; D003346:Corticotropin-Releasing Hormone; D010928:Placental Lactogen; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A