Stress-induced murine abortion associated with substance P-dependent alteration in cytokines in maternal uterine decidua.
Stress is known to induce abortions, but underlying mechanisms are unknown. Both alloimmunization and injection of antibody to the asialoGM1 determinant of natural killer cells have been shown to prevent stress-triggered abortion in mice. DBA/2J-mated CBA/J female mice were used to investigate the influence of stress during early gestation on systemic hormone levels and on cytokines in the decidua that are thought to be relevant to abortion in nonstress-related murine abortion. Lowered levels of progesterone did not occur as a result of stress. In stressed mice, increased levels of the abortogenic cytokine tumor necrosis factor alpha (TNF alpha) were associated with decreased levels of pregnancy-protective transforming growth factor beta 2-related suppressive activity in uterine decidua. In the alloimmunized animals where stress failed to boost the abortion rate, these effects were abrogated. Production of TNF alpha may be stimulated by the neurotransmitter substance P (SP); after injection of an SP receptor antagonist or SP-antibody, stress failed to increase the abortion rate above the background level. The increased levels of TNF alpha we observed in the stressed animals were completely abrogated in the animals that had received the SP receptor antagonist; stress also failed to decrease the pregnancy-protective suppressive activity in the decidua of these animals. The data indicate that stress may inhibit protective suppressor mechanisms and promote secretion of abortogenic cytokines such as TNF alpha via neurotransmitter SP.
Arck
P C
PC
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Merali
F S
FS
Stanisz
A M
AM
Stead
R H
RH
Chaouat
G
G
Manuel
J
J
Clark
D A
DA
D000022:Abortion, Spontaneous / Q000209:etiology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D005260:Female; D005327:Fetal Resorption; D007116:Immunization, Passive; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D064729:Neurokinin-1 Receptor Antagonists; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D064729:Neurokinin-1 Receptor Antagonists; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D011374:Progesterone