Effect of danazol on NK cells and cytokines in the mouse uterus

J Reprod Dev. 2007 Feb;53(1):87-94. doi: 10.1262/jrd.18074. Epub 2006 Nov 1.

Abstract

Danazol, which has been used as a medicine for endometriosis, has a valid effect in pretreatment of patients receiving in vitro fertilization and embryo transfer, although its reproductive mechanism remains unclear. BALB/c mice were subcutaneously injected with danazol for 2 weeks. Blood and uteri were collected and cytokines were assayed. Following danazol treatment, an increase in pregnancy ratio was evident that was accompanied by up-regulation in serum macrophage-colony stimulating factor (M-CSF). RT-PCR analysis revealed that expression of M-CSF and Ly49, a phenotypic marker of natural killer (NK) cells, was up-regulated in the uteri of the danazol-treated mice. In immunohistochemical analysis, M-CSF and Ly49, together with alpha5 integrin, were clearly detected in the endometrium of the danazol-treated mice with very similar pattern of localization. These results suggest that danazol has an effect to promote pregnancy that induces recruitment of NK cells and a concomitant increase in the expression of M-CSF and alpha5 integrin in the uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / blood*
  • Danazol / pharmacology*
  • Estrogen Antagonists / pharmacology*
  • Estrous Cycle / drug effects
  • Female
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Interleukin-4 / blood
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Macrophage Colony-Stimulating Factor / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pregnancy
  • Pregnancy Rate
  • Reproduction / drug effects
  • Uterus / cytology*
  • Uterus / immunology

Substances

  • Cytokines
  • Estrogen Antagonists
  • Interleukin-12
  • Interleukin-4
  • Macrophage Colony-Stimulating Factor
  • Interferon-gamma
  • Danazol