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Murine Stress‐triggered Abortion is Mediated by Increase of CD8 + TNF‐α + Decidual Cells via Substance P
Author(s) -
JOACHIM R.A.,
HILDEBRANDT M.,
ODER J.,
KLAPP B.F.,
ARCK P.C.
Publication year - 2001
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.8755-8920.2001.450506.x
Subject(s) - decidua , cd8 , endocrinology , medicine , decidual cells , cytokine , tumor necrosis factor alpha , degranulation , biology , flow cytometry , receptor , andrology , chemistry , immunology , pregnancy , immune system , fetus , placenta , genetics
PROBLEM: Stress is known to induce abortions in mice and humans. Increased levels of abortogenic type 1 helper T‐cell cytokines and decreased levels of pregnancy protective cytokines could be linked to stress‐triggered embryonic loss. Stress promotes neurotransmitter substance P (SP) release in tissues. SP increases the production of decidual tumor necrosis factor (TNF)‐α, whereby the phenotype of these TNF‐α‐producing cells is hypothetical. The objective of the present study was to identify decidual TNF‐α‐producing cell populations that are involved in stress‐induced murine abortion.
METHOD: DBA/2J‐mated CBA/J female mice were exposed to ultrasonic sound stress on day 5.5 of pregnancy. The mice were randomized and half were treated with the SP NK1‐receptor antagonist (SP‐RA) RP 67580 (200 μg/mouse). Frequency and cytokine profile of CD8 + cells were evaluated by immunohistochemistry and flow cytometry. Degranulation of uterine mast cells was examined histologically.
RESULTS: On day 13.5 of pregnancy, the uteri were removed and the resorption rate was calculated. A mean resorption rate of 38.4% was detected in stressed mice ( n =10) compared to 13.1% in non‐stressed control mice ( n =11, P <0.01). Injection of SP‐RA decreased the abortion rate to 18.4% in stressed mice ( n =19, P <0.01). Flow cytometry revealed a stress‐related increase of TNF‐α + /CD8 + decidual T cells, which could be abrogated by SP‐RA ( P <0.05). No significant differences could be observed in numbers of mast cells and total CD8 + cells in situ .
CONCLUSION: Our data suggest that stress‐triggered abortion is mediated by SP, and SP receptor blockade abrogates stress‐triggered abortion via reduced production of TNF‐α by CD8 + T cells.