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M. De, T. R. Sanford and G. W. Wood

Interleukin 1 (IL-1), IL-6 and tumour necrosis factor alpha (TNF-α) are expressed in the mouse uterus on days 1–3 of pregnancy. Cytokine production is temporally associated with the post-mating intrauterine acute inflammatory response. In this study, IL-1, IL-6 and TNF-α were detected in the uterus of pregnant mice from day 3 to day 9, using northern blotting, bioassays and immunocytochemistry. IL-1 bioactivity increased from a low concentration on day 3 to a peak between days 4 and 5 and decreased to low concentrations on days 7 and 8. Blastocyst implantation occurs late on day 4. IL-6 bioactivity was high from day 3 to day 9 and activity was maximal on days 5 and 6. TNF-α bioactivity increased from its lowest concentration on day 3 to a peak on day 8. Although changes in bioactivity concentrations occurred at different times from changes in mRNA concentrations, the changes were approximately parallel. Translation of mRNA into an immunologically detectable product was confirmed using immunocytochemistry with polyclonal anti-cytokine antibodies. We conclude that the cytokines IL-1, IL-6 and TNF-α are produced in the uterus during the periimplantation period of pregnancy in mice. Changes in cytokine concentrations suggested the existence of some form of regulated expression.

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T. R. Sanford, M. De and G. W. Wood

Summary. Morphological and immunohistochemical analyses have documented the development of an acute inflammatory response, marked by the early appearance of granulocytes and later infiltration of mononuclear cells, in the uterus immediately after mating in mice. The response peaked on Day 1 and subsided by Day 3. In the present study, RNAs for macrophage colony-stimulating factor (CSF-1) and granulocyte–macrophage colony-stimulating factor (GM-CSF) and for interleukin lα (IL-1α), IL-1 β, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were detected in uterine tissue on Day 1. With the exception of IL-6, which was higher on Day 3 than on Day 1, and IL-1α, which was not reduced on Day 2, concentrations of cytokine mRNA decreased to Day 3. No bioactivity was detected for GM-CSF, granulocyte colony-stimulating factor or IL-3, but CSF-1, IL-1, IL-6 and TNF-α were detected on Day 1 using bioassays. Changes in concentrations approximately paralleled those for mRNA. The concentrations of mRNA for CSF-1, IL-1, IL-6 and TNF-α were higher on Day 1 of pregnancy than in the uteri of cycling mice 24 h earlier. The data are consistent with previous morphological observations demonstrating the expression of an acute inflammatory response in the mouse uterus after mating. Further, the data demonstrate the expression of genes for CSF-1, GM-CSF, IL-1α, IL-1β, IL-6 and TNF-α is induced in the uterus during mating.

Keywords: mating; interleukin 1; interleukin 6; tumour necrosis factor alpha; colony-stimulating factors; mouse