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Updated: Oct 5, 2026
Isolation of Leukocytes from the Murine Tissues at the Maternal-Fetal Interface
Published on: May 21, 2015
Murine stress-triggered abortion is mediated by increase of CD8+ TNF-alpha+ decidual cells via substance P
R A Joachim1, M Hildebrandt, J Oder
1Department of Internal Medicine, Charité-Campus Virchow, Humboldt University, Berlin, Germany.
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)-alpha, whereby the phenotype of these TNF-alpha-producing cells is hypothetical. The objective of the present study was to identify decidual TNF-alpha-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 microg/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-alpha+/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-alpha by CD8+ T cells.
