Stress triggered abortions are associated with alterations of granulated cells in the decidua

PROBLEM: Stress is known to be abortogenic in animals and humans. An increased decidual release of cytokines such as TNF-α and reduction in TGF-β2-related immunosuppressive activity has been proposed as the triggering mechanism. Substance P released by nerves in endometrium/decidua has been found to be the key neurotransmitter in this pathway. It is still unclear which cells are stimulated by substance P to produce the increased TNF-α level. METHOD: As a measure of local activation, the granulation of granulated metrial gland (GMG) cells was measured by flow cytometry after sonic plus immobilization stress of mice or substance P treatment of GMG cells (both isolated GMG cells and GMG-cell containing decidua). TNF-α release from decidua and isolated GMG cells was investigated using a TNF-α bioassay. The degranulation of uterine mast cell, another potential source of TNF-α, was examined in situ by Toluidine blue staining. RESULTS: We observed a striking increase in percentage of degranulated mast cells (8% → 24%) in the uteri of stressed animals, whereas the granularity of GMG cells was decreased by stress but increased with treatment with substance P in vitro. Isolated GMG cells appeared to release in vitro cytotoxins active in the TNF-α bioassay, but the magnitude of this activity was not increased by stress or by substance P treatment. In contrast, disaggregated decidual tissue which is known to release increased amounts of TNF-α after stress, did increase activity in response to substance P in vitro. CONCLUSIONS: Uterine mast cells show activation as reflected by degranulation after stress exposure of pregnant mice and mast cells might be the cellular link between the neurotransmitter substance P and an increase in decidual TNF-α release that leads to abortion.