title: Downregulation of indoleamine 2, 3-dioxygenase expression in the villous stromal endothelial cells of placentas with preeclampsia.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: naoyuki@wakayama-med.ac.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Iwahashi
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: madoka-y@wakayama-med.ac.jp.
authors.forename: Madoka
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: sakiko-n@wakayama-med.ac.jp.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Nanjo
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: toujima@wakayama-med.ac.jp.
authors.forename: Saori
authors.initials: S
authors.lastname: Toujima
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: awako@wakayama-med.ac.jp.
authors.forename: Sawako
authors.initials: S
authors.lastname: Minami
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, 811-1 Kimiidera, Wakayama,641-0012, Japan. Electronic address: kazuino@wakayama-med.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ino
mesh_terms: D000328:Adult; D002824:Chorionic Villi / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005317:Fetal Growth Retardation / Q000276:immunology*; D006801:Humans; D006973:Hypertension; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D010920:Placenta / Q000473:pathology*; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011507:Proteinuria; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism* / Q000648:ultrastructure; D014327:Trophoblasts / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: 3-Dioxygenase; Fetal growth restriction; Indoleamine 2; Placenta; Preeclampsia