title: Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC).
abstract: OBJECTIVE
  To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in patients with early pregnancy loss compared with control patients with uncomplicated term delivery.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10).
  
  
  METHODS
  Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5-10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling.
  
  
  METHODS
  Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), galectin-14 (LGALS14), and placental growth factor (PGF).
  
  
  RESULTS
  The EVT purity was over 95% in all specimens, based on chorionic gonadotropin expression; however, the number of EVT cells obtained was significantly lower in women with EPL than the control group. There was a statistically significant elevation of AFP, ENG, and FLT-1, and statistically significant reduction of PAPP-A, LGALS14, and PGF in the EPL group compared with controls.
  
  
  CONCLUSIONS
  In this pilot study, EVT cells isolated by TRIC early in gestation exhibited altered protein expression patterns before an EPL compared with uncomplicated term pregnancies.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Rani
authors.initials: R
authors.lastname: Fritz
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Hamid-Reza
authors.initials: HR
authors.lastname: Kohan-Ghadr
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Bolnick
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Bolnick
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kilburn
authors.affiliation: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan.
authors.forename: Sascha
authors.initials: S
authors.lastname: Drewlo
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, Michigan; Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, Michigan; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. Electronic address: d.armant@wayne.edu.
authors.forename: D Randall
authors.initials: DR
authors.lastname: Armant
mesh_terms: D000022:Abortion, Spontaneous / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D010865:Pilot Projects; D011247:Pregnancy; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism*; D014463:Ultrasonography; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D000509:alpha-Fetoproteins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Early pregnancy loss; prenatal testing; trophoblast; uteroplacental insufficiency