Tumor Necrosis Factor‐α mRNA‐Positive Cells in Spontaneous Resorption in Rodents
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abstract
PROBLEM: It has been proposed that high rates of resorption/spontaneous abortion may result from interaction in the decidua of γ‐interferon‐producing natural killer (NK) cells and tumor necrosis factor (TNF)‐α‐producing macrophages. An increased release of TNF‐α from placental tissue of resorptions has been reported, but macrophages producing TNF‐α have so far not been demonstrated at the feto‐maternal interface. Therefore, we have sought to identify TNF‐α‐producing cells by in situ hybridization at the feto‐maternal interface in two inbred, well‐characterized, and stable strains of laboratory rodents with high and low resorption rates.METHOD OF STUDY: Pregnant DBA/2‐mated CBA/J mice with a resorption rate of 20% to 30% (dependent on NK cells and macrophages) and diabetes‐resistant Bio‐Breeding/ Edinburgh (DR‐BB/E) rats with low resorption rates (presumed to result from chromosomal abnormalities) were studied. AsialoGMl+ cells were detected by immunohistochemistry, and TNF‐α mRNA+ cells were detected by in situ hybridization.RESULTS: TNF‐α mRNA+ cells were detected in DBA/2‐mated CBA/J mice at the time of resorption but only at the trophoblast‐decidual junction. AsialoGM1+ cells were present in decidua, as assessed by immunohistochemistry, but few if any gave a positive signal for TNF‐α. In rat resorptions, TNF‐α mRNA‐positive cells were present within the yolk sac and in contact with the trophoblast, but not at the trophoblast‐decidual junction. In neither species did a significant accumulation of detectable TNF‐α mRNA+ cells occur before the usual time of onset of resorption.CONCLUSIONS: In the DBA/2‐mated CBA/J mouse, the removal of the placenta is associated with removal of a thin rim of adherent decidua similar to the location of the TNF‐α mRNA+ cells detected in this study. Our data suggest that increased TNF‐α in tissues associated with failing feto‐placental units may arise from infiltration/activation of scavenger cells from decidua that are likely to be macrophages. Local TNF‐α production in decidua, which occurs as a prelude to resorption in the CBA x DBA/2 model, could not be detected due to the insensitivity of the TNF‐α probe we used; the release of TNF‐α from decidual tissue left after the removal of the placenta does not differ between resorbing and healthy implant sites. AsialoGM1+ cells did not seem to be major producers of TNF‐α. TNF‐α mRNA+ cells in a low rate of resorption (rat) model were only found on the fetal side of the trophoblast, and they may also represent a macrophage response (to dying embryo tissue) derived from a nondecidual source. The location of TNF‐α mRNA+ cells may identify distinct and different mechanisms of resorption in rodents.
