Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001 Fuqiang Road, Futian District, Shenzhen, 518045, China.
Reprod Sci. 2020 Aug;27(8):1656-1664. doi: 10.1007/s43032-020-00196-5.
Indoleamine 2, 3-dioxygenase (IDO), an immunosuppressive enzyme that mediates the conversion of tryptophan to kynurenine, was shown to play a key role in placental development during normal pregnancy. However, little is known about the pattern of IDO expression in the endometrium and its attendant functional significance in pregnancies complicated with recurrent miscarriage (RM). Immunohistochemical studies of IDO, Foxp3, CD56, and CD163 expression were performed in endometrial samples from women with RM and healthy fertile controls. Our study found that IDO was localized in glandular epithelial cells, surface epithelial cells, and a small number of cells within the stromal compartment (including stromal cells and leukocytes) in endometrium. Indoleamine 2, 3-dioxygenase expression in the RM group was significantly lower than control group. The Foxp3 and CD56 expression were significantly increased with the elevated IDO expression in controls but not in RM. The percentage of Foxp3 + Tregs was significantly correlated with the level of IDO expression in the control group. Comparatively, no correlation was found between the percentage of CD56 + cells, CD163 + cells, and the level of IDO expression, no matter in controls and RM patients. This study demonstrated that the downregulation of IDO expression and noncoordinated association between IDO and other endometrial immune cells were associated with RM. Our findings provide insights into the contribution of IDO in immune regulation to maintain normal pregnancy, which could be used to develop potential therapeutic methods for RM.
色氨酸 2,3-双加氧酶(IDO)是一种免疫抑制酶,可介导色氨酸转化为犬尿氨酸,它在正常妊娠期间胎盘发育中发挥关键作用。然而,关于 IDO 在子宫内膜中的表达模式及其在复发性流产(RM)合并妊娠中的伴随功能意义知之甚少。我们对 RM 患者和健康生育对照组的子宫内膜样本进行了 IDO、Foxp3、CD56 和 CD163 表达的免疫组织化学研究。我们的研究发现 IDO 定位于子宫内膜的腺上皮细胞、表面上皮细胞和基质腔中的少量细胞(包括基质细胞和白细胞)。RM 组 IDO 的表达明显低于对照组。在对照组中,随着 IDO 表达的升高,Foxp3 和 CD56 的表达显著增加,但在 RM 中则不然。Foxp3+Tregs 的百分比与对照组 IDO 表达水平显著相关。相比之下,在对照组和 RM 患者中,均未发现 CD56+细胞和 CD163+细胞的百分比与 IDO 表达水平之间存在相关性。本研究表明,IDO 表达的下调以及 IDO 与其他子宫内膜免疫细胞之间的不协调关联与 RM 有关。我们的研究结果为 IDO 在维持正常妊娠的免疫调节中的作用提供了新的认识,这可能为 RM 的潜在治疗方法的开发提供依据。