Decidualization is essential for successful pregnancy in rodents and primates. Although L-Tryptophan and its metabolites are essential for mammalian pregnancy, the underlying mechanism is poorly defined. We explored effects of tryptophan and kynurenine on human in vitro decidualization in human endometrial stromal cell line and primary endometrial stromal cells. Tryptophan significantly stimulates the expression of prolactin and insulin growth factor binding protein 1, reliable markers for human decidualization. When stromal cells are treated with tryptophan, tryptophan hydroxylase-1 remains unchanged, but indoleamine 2,3-dioxygenase 1 is significantly increased, suggesting tryptophan is mainly metabolized through kynurenine pathway. Kynurenine significantly stimulates insulin growth factor binding protein 1 expression. Aryl hydrocarbon receptor and its target genes (P450 1A1 and P450 1B1) are significantly increased by tryptophan and kynurenine. The induction of tryptophan and kynurenine on insulin growth factor binding protein 1 is abrogated by CH223191, an aryl hydrocarbon receptor inhibitor. Cytochrome P450 1A1 and P450 1B1 catalyze the oxidative metabolism of estradiol to catechol estrogens (2-hydroxy estradiol and 4-hydroxy estradiol), respectively. Insulin growth factor binding protein 1 is up-regulated by 2-hydroxy estradiol and 4-hydroxy estradiol. Interferon-γ significantly induces the expression of indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor and insulin growth factor binding protein 1. All the data are also verified in primary human stromal cells. Our data indicate that Interferon-γ-induced kynurenine pathway promotes human decidualization via aryl hydrocarbon receptor signaling.

蜕膜对于啮齿动物和灵长类动物的成功怀孕至关重要。尽管 L-色氨酸及其代谢物对哺乳动物妊娠至关重要，但其潜在机制尚不清楚。我们探讨了色氨酸和犬尿氨酸对人子宫内膜基质细胞系和原代子宫内膜基质细胞体外蜕膜化的影响。色氨酸显着刺激催乳素和胰岛素生长因子结合蛋白 1 的表达，这是人类蜕膜化的可靠标志物。当基质细胞用色氨酸处理时，色氨酸羟化酶-1保持不变，但吲哚胺2,3-双加氧酶1显着升高，表明色氨酸主要通过犬尿氨酸途径代谢。Kynurenine 显着刺激胰岛素生长因子结合蛋白 1 的表达。色氨酸和犬尿氨酸显着增加芳烃受体及其靶基因（P450 1A1 和 P450 1B1）。芳烃受体抑制剂 CH223191 消除了色氨酸和犬尿氨酸对胰岛素生长因子结合蛋白 1 的诱导作用。细胞色素 P450 1A1 和 P450 1B1 分别催化雌二醇氧化代谢为儿茶酚雌激素（2-羟基雌二醇和 4-羟基雌二醇）。胰岛素生长因子结合蛋白 1 被 2-羟基雌二醇和 4-羟基雌二醇上调。干扰素-γ 显着诱导吲哚胺 2,3-双加氧酶 1、芳烃受体和胰岛素生长因子结合蛋白 1 的表达。所有数据也在原代人基质细胞中得到验证。