title: Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy.
abstract: Remodeling of uterine spiral arteries is critical for the continuation of a successful pregnancy. Uterine natural killer (uNK) cells are the predominant leukocyte population in the early pregnant decidua, and a role for these cells in spiral artery remodeling in pregnancy has been suggested. Angiogenic growth factors were measured in isolated uNK and total (unseparated) decidual cells (8-10 or 12-14 weeks gestation, n=5 each gestational age) after culture for 48 h. Angiopoietin (Ang)1, placental growth factor, transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF)-C were measured by enzyme-linked immunosorbent assay. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. Levels of Ang2, ICAM-1, and KGF, secreted by the total decidual fraction, decreased with increasing gestational age. uNK levels of Ang2 and VEGF-C also decreased with increasing gestational age. At 8-10 weeks gestation, there was no difference in the level of Ang1, Ang2, TGF-beta1, and VEGF-C secreted by uNK cells and the total decidual fraction. At 12-14 weeks, uNK cells secreted significantly lower levels of VEGF-C than the total decidual fraction. Early pregnancy decidua is a major source of angiogenic growth factors whose levels decrease with increasing gestational age, suggesting that they may play a role in spiral artery remodeling. uNK cells appear to be a prominent source of Ang1, Ang2, TGF-beta1, and VEGF-C within the placental bed.
authors.affiliation: School of Surgical and Reproductive Sciences, 3rd Floor, William Leech Building, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK. g.e.lash@ncl.ac.uk
authors.forename: Gendie E
authors.initials: GE
authors.lastname: Lash
authors.forename: Barbara
authors.initials: B
authors.lastname: Schiessl
authors.forename: Maureen
authors.initials: M
authors.lastname: Kirkley
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Innes
authors.forename: Alix
authors.initials: A
authors.lastname: Cooper
authors.forename: Roger F
authors.initials: RF
authors.lastname: Searle
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Robson
authors.forename: Judith N
authors.initials: JN
authors.lastname: Bulmer
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014599:Uterus / Q000166:cytology* / Q000276:immunology
chemical_list: D042501:Angiogenic Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1