STRESS-INDUCED MURINE ABORTION ASSOCIATED WITH SUBSTANCE BETA-DEPENDENT ALTERATION IN CYTOKINES IN MATERNAL UTERINE DECIDUA
STRESS-INDUCED MURINE ABORTION ASSOCIATED WITH SUBSTANCE BETA-DEPENDENT ALTERATION IN CYTOKINES IN MATERNAL UTERINE DECIDUA
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DOI：
10.1095/biolreprod53.4.814
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发表时间：
1995-10-01
影响因子：
3.6
通讯作者：
CLARK, DA
中科院分区：
文献类型：
--
作者：
ARCK, PC;MERALI, FS;CLARK, DA
众所周知，压力会导致流产，但潜在的机制尚不清楚。同种异体免疫和注射针对自然杀伤细胞的asialo GM1决定簇的抗体都被证明可以防止应激引发的小鼠流产。采用DBA/SJ交配的CBA/J雌性小鼠，研究了妊娠早期应激对系统激素水平和蜕膜细胞因子的影响，这些细胞因子被认为与非应激相关流产有关。黄体酮水平的降低并不是由于压力造成的。在应激小鼠中，流产细胞因子肿瘤坏死因子α(TNFα)水平的增加与子宫蜕膜中与妊娠保护性转化生长因子β2相关的抑制活动水平降低有关。在应激未能提高堕胎率的同种免疫动物中，这些影响被取消。神经递质P物质(SP)可刺激肿瘤坏死因子α的产生；注射SP受体拮抗剂或SP抗体后，应激不能增加高于本底水平的流产率。在接受SP受体拮抗剂的动物中，我们观察到的应激动物体内增加的肿瘤坏死因子α水平被完全消除；应激也没有减少这些动物蜕膜中的妊娠保护抑制活性。结果表明，应激可能通过神经递质SP抑制保护性抑制机制，促进流产细胞因子如肿瘤坏死因子α的分泌。
Stress is known to induce abortions, but underlying mechanisms are unknown. Both alloimmunization and injection of antibody to the asialo GM1 determinant of natural killer cells have been shown to prevent stress-triggered abortion in mice. DBA/SJ-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.