Uterine natural killer cells severely decrease in number at gestation day 6 in mice

Biol Reprod. 2013 Oct 31;89(4):101. doi: 10.1095/biolreprod.113.109009. Print 2013 Oct.


Uterine natural killer (uNK) cells remarkably increase in number after implantation. NK cells or their precursors migrate from the blood stream and contribute to the increase. However, the contribution of uNK cells present in the virgin uterus has been unclear. To elucidate this issue, we examined uterine leukocyte subsets during pregnancy in BALB/c mice. The most dramatic change was the massive decrease in CD11b⁻ or Gr-1⁻ cells at gestation day (gd) 6. Uterine NK cells at gd 0 were CD11b⁻, and severely decreased at gd 6. The decrease was selective, and the proportion of other cells examined did not decrease. Uterine NK cells almost recovered at gd 12. These cells at gd 12 were more mature and/or activated in terms of expression of CD11b, CD27, CD127, or B220 than at gd 0. CXCL12 expression was observed on uterine cells at gd 0 or 6, but not at gd 12, whereas CXCR4 was detected on uNK cells at gds 0 and 12. A much higher expression of IL-15 in uterine cells or interferon-gamma expression in uNK cells was observed at gd 12 than at gd 0. IL-15 receptor alpha chain was detected on uNK cells at gd 12, but not at gd 0. Taken together, these findings were consistent with our interpretation that uNK cells present at gd 0 do not contribute to the increase of uNK cell number after implantation, and NK cells or their precursors migrate into the uterus, mature, and produce interferon-gamma to support pregnancy.

Keywords: guinea pigs; implantation; mice; natural killer cell; pregnancy; rodents (rats; uterus; voles).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Chemokine CXCL12 / metabolism
  • Embryo Implantation
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation Mediators / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Luteal Phase
  • Mice
  • Mice, Inbred BALB C
  • Placentation
  • Pregnancy / physiology*
  • Pregnancy Maintenance*
  • Receptors, CXCR4 / metabolism
  • Specific Pathogen-Free Organisms
  • Uterus / cytology
  • Uterus / immunology*
  • Uterus / metabolism


  • Antigens, CD
  • Biomarkers
  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Inflammation Mediators
  • Receptors, CXCR4