Mouse model for allogeneic immune reaction against fetus recapitulates human pre-eclampsia

Haruki Nishizawa, Kiyoshi Hasegawa, MacHiko Suzuki, Yumiko Achiwa, Takema Kato, Kuniaki Saito, Hiroki Kurahashi, Yasuhiro Udagawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Aim: 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.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Obstetrics and Gynaecology Research
Volume34
Issue number1
DOIs
Publication statusPublished - 01-02-2008

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Pre-Eclampsia
Fetus
Placenta
Mothers
Proteinuria
Tryptophan
Hypertension
T-Lymphocytes
Messenger RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynaecology

Cite this

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title = "Mouse model for allogeneic immune reaction against fetus recapitulates human pre-eclampsia",
abstract = "Aim: 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.",
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Mouse model for allogeneic immune reaction against fetus recapitulates human pre-eclampsia. / Nishizawa, Haruki; Hasegawa, Kiyoshi; Suzuki, MacHiko; Achiwa, Yumiko; Kato, Takema; Saito, Kuniaki; Kurahashi, Hiroki; Udagawa, Yasuhiro.

In: Journal of Obstetrics and Gynaecology Research, Vol. 34, No. 1, 01.02.2008, p. 1-6.

Research output: Contribution to journalArticle

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AU - Nishizawa, Haruki

AU - Hasegawa, Kiyoshi

AU - Suzuki, MacHiko

AU - Achiwa, Yumiko

AU - Kato, Takema

AU - Saito, Kuniaki

AU - Kurahashi, Hiroki

AU - Udagawa, Yasuhiro

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