Iwahashi Naoyuki, Yamamoto Madoka, Nanjo Sakiko, Toujima Saori, Minami Sawako, Ino Kazuhiko
Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan.
J Reprod Immunol. 2017 Feb;119:54-60. doi: 10.1016/j.jri.2017.01.003. Epub 2017 Jan 23.
Previous studies have shown that indoleamine 2, 3-dioxygenase (IDO), an immunosuppressive enzyme that converts tryptophan to kynurenine, is expressed in the placenta and might play a role in the maintenance of pregnancy, although its associations with the pathogeneses of preeclampsia (PE) and fetal growth restriction (FGR) remain unclear. The objective of this study was to investigate the differences in IDO expression among normal, PE, and FGR placentas, and the associations between IDO expression and clinical symptoms, or the expression of fms-like tyrosine kinase receptor-1 (Flt-1).
Immunohistochemical studies of IDO and Flt-1 expression were performed in human placentas that were complicated with FGR alone (n=19), PE alone (n=20), or both PE and FGR (n=39), and gestational age-matched controls (n=23).
It was found that IDO was expressed on endothelial cells in the villous stroma, while Flt-1 was located on trophoblast cells. The IDO expression level of the PE alone group was significantly lower than those of the FGR alone and control groups. The IDO expression of the PE+FGR group was significantly lower than that of the FGR alone group. Lower IDO expression was significantly correlated with more severe maternal hypertension or proteinuria in PE patients, who exhibited higher Flt-1 expression. The late onset PE patients exhibited significantly lower IDO expression than the early onset PE patients.
This study demonstrated that the downregulation of IDO expression on the endothelial cells of the villous stroma was associated with PE, but not FGR, suggesting that IDO might be involved in the pathophysiology of PE.
先前的研究表明，吲哚胺2,3-双加氧酶（IDO）是一种将色氨酸转化为犬尿氨酸的免疫抑制酶，在胎盘中表达，可能在维持妊娠中发挥作用，尽管其与子痫前期（PE）和胎儿生长受限（FGR）发病机制之间的关联仍不清楚。本研究的目的是调查正常胎盘、PE胎盘和FGR胎盘中IDO表达的差异，以及IDO表达与临床症状或fms样酪氨酸激酶受体-1（Flt-1）表达之间的关联。
对仅合并FGR（n=19）、仅合并PE（n=20）或同时合并PE和FGR（n=39）的人胎盘以及孕周匹配的对照组（n=23）进行IDO和Flt-1表达的免疫组织化学研究。
发现IDO在绒毛间质的内皮细胞上表达，而Flt-1位于滋养层细胞上。仅PE组的IDO表达水平显著低于仅FGR组和对照组。PE+FGR组的IDO表达显著低于仅FGR组。IDO表达降低与PE患者更严重的母体高血压或蛋白尿显著相关，这些患者表现出更高的Flt-1表达。晚发型PE患者的IDO表达显著低于早发型PE患者。
本研究表明，绒毛间质内皮细胞上IDO表达的下调与PE有关，而与FGR无关，提示IDO可能参与了PE的病理生理过程。
