Rg. Lea et al., TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA-POSITIVE CELLS IN SPONTANEOUS RESORPTION IN RODENTS, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 39(1), 1998, pp. 50-57
PROBLEM: It has been proposed that high rates of resorption/spontaneou
s abortion may result from interaction in the decidua of gamma-interfe
ron-producing natural killer (NK) cells and tumor necrosis factor (TNF
)-alpha-producing macrophages. An increased release of TNF-alpha from
placental tissue of resorptions has been reported, but macrophages pro
ducing TNF-alpha have so far not been demonstrated at the fete-materna
l interface. Therefore, we have sought to identify TNF-alpha-producing
cells by in situ hybridization at the fete-maternal interface in two
inbred, well-characterized, and stable strains of laboratory rodents w
ith high and low resorption rates. METHOD OF STUDY: Pregnant DBA/2-mat
ed CBA/J mice with a resorption rate of 20% to 30% (dependent on NK ce
lls and macrophages) and diabetes-resistant Bio-Breeding/Edinburgh (DR
-BB/E) rats with low resorption rates (presumed to result from chromos
omal abnormalities) were studied. AsialoGM1(+) cells were detected by
immunohistochemistry, and TNF-alpha mRNA(+) cells were detected by in
situ hybridization. RESULTS: TNF-alpha mRNA(+) cells were detected in
DBA/2-mated CBA/J mice at the time of resorption but only at the troph
oblast-decidual junction. AsialoGM1(+) cells were present in decidua,
as assessed by immunohistochemistry, but few if any gave a positive si
gnal for TNF-alpha. In rat resorptions, TNF-alpha 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-alpha 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 re
moval of a thin rim of adherent decidua similar to the location of the
TNF-alpha mRNA(+) cells detected in this study. Our data suggest that
increased TNF-alpha in tissues associated with failing fete-placental
units may arise from infiltration/activation of scavenger cells from
decidua that are likely to be macrophages. Local TNF-alpha 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-alph
a probe we used; the release of TNF-alpha from decidual tissue left af
ter the removal of the placenta does not differ between resorbing and
healthy implant sites. AsialoGM1(+) cells did not seem to be major pro
ducers of TNF-alpha. TNF-alpha mRNA(+) cells in a low rate of resorpti
on (rat) model were only found on the fetal side of the trophoblast, a
nd they may also represent a macrophage response (to dying embryo tiss
ue) derived from a nondecidual source. The location of TNF-alpha mRNA(
+) cells may identify distinct and different mechanisms of resorption
in rodents.