STRESS-INDUCED MURINE ABORTION ASSOCIATED WITH SUBSTANCE BETA-DEPENDENT ALTERATION IN CYTOKINES IN MATERNAL UTERINE DECIDUA

Stress is known to induce abortions, but underlying mechanisms are unk nown. Both alloimmunization and injection of antibody to the asialo GM 1 determinant of natural killer cells have been shown to prevent stres s-triggered abortion in mice. DBA/SJ-mated CBA/J female mice were used to investigate the influence of stress during early gestation on syst emic hormone levels and on cytokines in the decidua that are thought t o be relevant to abortion in nonstress-related murine abortion. Lowere d levels of progesterone did not occur as a result of stress. In stres sed mice, increased levels of the abortogenic cytokine tumor necrosis factor alpha (TNF alpha) were associated with decreased levels of preg nancy-protective transforming growth factor beta 2-related suppressive activity in uterine decidua. In the alloimmunized animals where stres s failed to boost the abortion rate, these effects were abrogated. Pro duction of TNF alpha may be stimulated by the neurotransmitter substan ce P (SP); after injection of an SP receptor antagonist or SP-antibody , stress failed to increase the abortion rate above the background lev el. The increased levels of TNF alpha we observed in the stressed anim als were completely abrogated in the animals that had received the SP receptor antagonist; stress also failed to decrease the pregnancy-prot ective 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 neuro transmitter SP.