Stress Triggered Abortions Are Associated With Alterations of Granulated Cells in the Decidua
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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% r̊ 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.
