title: Stress triggered abortions are associated with alterations of granulated cells into the decidua.
abstract: OBJECTIVE
  Stress is known to be abortogenic in animals and humans. An increased decidual release of cytokines such as TNF-alpha and reduction in TGF-beta 2-related immunosuppressive activity has been proposed as the triggering mechanism. Substance P release 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-alpha level.
  
  
  METHODS
  As a measure of local activation, the granulation of granulated material 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-alpha release from decidua and isolated GMG cells was investigated using a TNF-alpha bioassay. The degranulation of uterine mast cell, another potential source of TNF-alpha, 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-alpha bioassay, but the magnitude of this activity was not increase by stress or by substance P treatment. In contrast, disaggregated decidual tissue which is known to release increased amounts of TNF-alpha 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 increase in decidual TNF-alpha release that leads to abortion.
authors.affiliation: McMaster University, Hamilton, Ontario, Canada.
authors.forename: U R
authors.initials: UR
authors.lastname: Markert
authors.forename: P C
authors.initials: PC
authors.lastname: Arck
authors.forename: B A
authors.initials: BA
authors.lastname: McBey
authors.forename: J
authors.initials: J
authors.lastname: Manuel
authors.forename: B A
authors.initials: BA
authors.lastname: Croy
authors.forename: J S
authors.initials: JS
authors.lastname: Marshall
authors.forename: G
authors.initials: G
authors.lastname: Chaouat
authors.forename: D A
authors.initials: DA
authors.lastname: Clark
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D000818:Animals; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006636:Histamine Release; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008791:Metrial Gland / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D013312:Stress, Physiological / Q000209:etiology / Q000276:immunology*