title: Mouse model for allogeneic immune reaction against fetus recapitulates human pre-eclampsia.
abstract: OBJECTIVE
  We have previously demonstrated that mRNA expression and enzyme activity levels of placental indoleamine 2,3-dioxygenase (IDO), which degrades L-tryptophan and blocks the proliferation of T cells, are significantly low in patients with severe pre-eclampsia. From this observation, we hypothesized that induction of maternal allogeneic immune reaction by reduced IDO activity is one of the causes of pre-eclampsia.
  
  
  METHODS
  To examine this hypothesis, we administered an IDO inhibitor to pregnant female mice carrying allogeneic concepti. Since administration of an IDO inhibitor to pregnant mice starting at E4.5 is already reported to cause allogeneic fetal rejection, we modified the regimen and started the administration at E6.5 when the fetus and placenta have already been established.
  
  
  RESULTS
  Pregnant mice treated with an IDO inhibitor developed high blood pressure and proteinuria in addition to local circulation impairment in the placenta, which is analogous to the lesions that are characteristic of human pre-eclampsia. In contrast, pregnant mice carrying syngeneic concepti did not manifest such symptoms.
  
  
  CONCLUSIONS
  Our findings reveal a pivotal role for IDO activity in the etiology of pre-eclampsia. These data also lend support to the current hypothesis that pre-eclampsia is one of the possible manifestations of a maternal immunological reaction against an allogeneic fetus.
authors.affiliation: Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. nharuki@fujita-hu.ac.jp
authors.forename: Haruki
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Machiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Achiwa
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000503:physiopathology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C028129:tryptophan methyl ester; D014364:Tryptophan