College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountain Region, College of Animal Science, Guizhou University, Guiyang 550025, China.
Int J Mol Sci. 2023 Feb 5;24(4):3163. doi: 10.3390/ijms24043163.
Decidualization is necessary for the successful establishment of early pregnancy in rodents and humans. Disturbed decidualization results in recurrent implantation failure, recurrent spontaneous abortion, and preeclampsia. Tryptophan (Trp), one of the essential amino acids in humans, has a positive effect on mammalian pregnancy. Interleukin 4-induced gene 1 (IL4I1) is a recently identified enzyme that can metabolize L-Trp to activate aryl hydrocarbon receptor (AHR). Although IDO1-catalyzed kynurenine (Kyn) from Trp has been shown to enhance human in vitro decidualization via activating AHR, whether IL4I1-catalyzed metabolites of Trp are involved in human decidualization is still unknown. In our study, human chorionic gonadotropin stimulates IL4I1 expression and secretion from human endometrial epithelial cells through ornithine decarboxylase-induced putrescine production. Either IL4I1-catalyzed indole-3-pyruvic acid (I3P) or its metabolite indole-3-aldehyde (I3A) from Trp is able to induce human in vitro decidualization by activating AHR. As a target gene of AHR, Epiregulin induced by I3P and I3A promotes human in vitro decidualization. Our study indicates that IL4I1-catalyzed metabolites from Trp can enhance human in vitro decidualization through AHR-Epiregulin pathway.
蜕膜化对于啮齿动物和人类早期妊娠的成功建立是必要的。蜕膜化紊乱会导致反复着床失败、反复自然流产和子痫前期。色氨酸（Trp）是人类必需氨基酸之一，对哺乳动物妊娠有积极影响。白细胞介素 4 诱导基因 1（IL4I1）是一种新发现的酶，可代谢 L-Trp 以激活芳香烃受体（AHR）。尽管 IDO1 催化的色氨酸（Trp）衍生的犬尿氨酸（Kyn）已被证明通过激活 AHR 增强了人离体蜕膜化，但 Trp 的 IL4I1 催化代谢物是否参与人蜕膜化尚不清楚。在我们的研究中，人绒毛膜促性腺激素通过鸟氨酸脱羧酶诱导腐胺产生来刺激人子宫内膜上皮细胞中 IL4I1 的表达和分泌。色氨酸（Trp）经 IL4I1 催化生成的吲哚-3-丙酮酸（I3P）或其代谢物吲哚-3-乙醛（I3A）均可通过激活 AHR 诱导人离体蜕膜化。作为 AHR 的靶基因，I3P 和 I3A 诱导的 Epiregulin 促进人离体蜕膜化。我们的研究表明，Trp 的 IL4I1 催化代谢物可通过 AHR-Epiregulin 途径增强人离体蜕膜化。
