PROBLEM: 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. METHOD: 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.
PROBLEM: 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. METHOD: 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: Eva Patak; M Luz Candenas; Jocelyn N Pennefather; Sebastian Ziccone; Alison Lilley; Julio D Martín; Carlos Flores; Antonio G Mantecón; Margot E Story; Francisco M Pinto Journal: Br J Pharmacol Date: 2003-06 Impact factor: 8.739
Authors: G Chaouat; E Menu; B Mognetti; M Moussa; V Cayol; Y Mostefaoui; S Dubanchet; P Khadel; J L Voluménie; C B Rongiéres; G L Delage Journal: Infect Dis Obstet Gynecol Date: 1997