title: A distinct microvascular endothelial gene expression profile in severe IUGR placentas.
abstract: The placental microvasculature is essential for efficient transfer of gases, nutrients and waste between the mother and fetus. Microvascular hypoplasia of the terminal villi is a common pathology in severe Intra Uterine Growth Restriction (IUGR). We used novel methods to obtain placental micro-vascular endothelial cells (PlMEC) from preterm control placentas (n = 3) and placentas from pregnancies with severe IUGR (n = 6) with absent or reversed end-diastolic velocity in the umbilical artery. Distal placental villous tissue was collected to enrich for intermediate and terminal villi. Tissue was digested and PlMEC positively selected using tocosylated magnetic Dynabeads labeled with Human Endothelial Antigen lectin. The purity of the PlMEC (94 ± 2 SD %) was assessed by CD31 and vimentin immunocytochemistry. RNA was extracted from the PlMEC samples and subjected to Affymetrix microarray analysis (U133Plus2 array chips). Comparison of preterm and IUGR PlMEC gene expression profiles identified BTNL9 and NTRK2 transcripts to be upregulated and SAA1 and SLAMF1 transcripts to be downregulated in all 6 IUGR cases relative to preterm controls. A third downregulated gene GNAS was identified to be near significance. Changes were demonstrated to be significant at the mRNA level by Real Time PCR in the PlMEC samples. Changes in the IUGR endothelium were confirmed at the protein level by immunohistochemistry for the 3 with available antibodies. We used a tissue microarray constructed from an independent cohort of placental samples from severe IUGR (n = 7), preeclamptic (n = 7), preterm control (n = 6) and term control (n = 6) pregnancies. Results confirmed differential endothelial expression of BTNL9, NTRK2 and SLAMF1 in IUGR versus preterm and term samples. These studies are the first to characterize PlMEC gene expression profiles thus we have advanced our understanding of the molecular basis of placental micro-vascular pathophysiology in fetal growth restriction.
authors.affiliation: Research Centre for Women's and Infants' Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde St, Toronto, Ontario, Canada M5T 3H7. dunk@lunenfeld.ca
authors.forename: C E
authors.initials: CE
authors.lastname: Dunk
authors.forename: A M
authors.initials: AM
authors.lastname: Roggensack
authors.forename: B
authors.initials: B
authors.lastname: Cox
authors.forename: J E
authors.initials: JE
authors.lastname: Perkins
authors.forename: F
authors.initials: F
authors.lastname: Åsenius
authors.forename: S
authors.initials: S
authors.lastname: Keating
authors.forename: R
authors.initials: R
authors.lastname: Weksberg
authors.forename: J C P
authors.initials: JC
authors.lastname: Kingdom
authors.forename: S L
authors.initials: SL
authors.lastname: Adamson
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000071797:Butyrophilins; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000098:blood supply* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C573074:BTNL9 protein, human; D000071797:Butyrophilins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C521404:SAA1 protein, human; C000604059:SLAMF1 protein, human; D000685:Serum Amyloid A Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D020813:Receptor, trkB