Li Dang-Dang, Liu Xin-Yuan, Guo Chuan-Hui, Yue Liang, Yang Zhan-Qing, Cao Hang, Guo Bin, Yue Zhan-Peng
College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China.
In Vitro Cell Dev Biol Anim. 2015 Mar;51(3):264-72. doi: 10.1007/s11626-014-9833-3. Epub 2014 Nov 19.
Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.
吲哚胺 2,3-双加氧酶 2（Ido2）参与色氨酸分解代谢和免疫，但对其生理功能仍知之甚少。本研究旨在检测围植入期小鼠子宫中 Ido2 基因的表达及调控。结果显示，Ido2 mRNA 在妊娠第 4 天和延迟着床子宫中高表达。在妊娠第 5 - 8 天，子宫中 Ido2 表达水平较低。同时，Ido2 mRNA 在蜕膜化子宫中也低表达。在子宫基质细胞中，8-溴环磷腺苷（8-Br-cAMP）可抑制 Ido2 mRNA 的表达。此外，用雌激素和孕激素处理基质细胞后，Ido2 mRNA 表达逐渐降低，并在 96 小时达到最低点。进一步研究发现，在体外蜕膜化过程中，Ido2 过表达可下调蜕膜化标记基因催乳素（PRL）、胰岛素样生长因子结合蛋白 1（IGFBP1）和蜕膜蛋白（Dtprp）的表达，而用 1-甲基色氨酸（D-1-MT）抑制 Ido2 则可上调这些标记基因的表达。在体外蜕膜化过程中，Ido2 过表达可抑制子宫基质细胞增殖，并提高 Bax 和基质金属蛋白酶 2（MMP2）基因的表达。相反，Ido2 抑制剂 D-1-MT 可增强基质细胞增殖和 Bcl2 基因表达，但降低 Bax/Bcl ratio。在子宫基质细胞中，雌激素和孕激素可诱导 Ido2 mRNA 的表达。这些数据表明，Ido2 可能对小鼠胚胎着床和蜕膜化很重要。
