Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy

J Leukoc Biol. 2006 Sep;80(3):572-80. doi: 10.1189/jlb.0406250. Epub 2006 Jun 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / genetics*
  • Angiogenic Proteins / metabolism
  • Female
  • Gene Expression Regulation* / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Pregnancy Trimester, First
  • Pregnancy Trimester, Second
  • Pregnancy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism
  • Uterus / cytology*
  • Uterus / immunology


  • Angiogenic Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta1