Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes

Mark K. Santillan, Christopher J. Pelham, Pimonrat Ketsawatsomkron, Donna A. Santillan, Deborah R. Davis, Eric J. Devor, Katherine N. Gibson-Corle, Sabrina M. Scroggins, Justin L. Grobe, Baoli Yang, Steven K. Hunter, Curt D. Sigmund

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Preeclampsia is a cardiovascular disorder of late pregnancy that is, commonly characterized by hypertension, renal structural damage and dysfunction, and fetal growth restriction. Prevailing etiologic models of this disorder include T-cell dysfunction as an initiating cause of preeclampsia. Indoleamine 2,3-dioxygenase (IDO), an enzyme that mediates the conversion of tryptophan to kynurenine, has been linked to preeclampsia in humans, and is known to regulate T-cell activity and an endothelial-derived relaxing factor. To test the hypothesis that IDO is causally involved in the pathogenesis of preeclampsia, mice deficient for IDO (IDO-KO) were generated on a C57BL/6 background. IDO-KO and wild-type C57BL/6 mice were bred, and preeclampsia phenotypes were evaluated during pregnancy. Pregnant IDO-KO mice exhibited pathognomonic renal glomerular endotheliosis, proteinuria, pregnancy-specific endothelial dysfunction, intrauterine growth restriction, and mildly elevated blood pressure compared to wild-type mice. Together these findings highlight an important role for IDO in the generation of phenotypes typical of preeclampsia. Loss of IDO function may represent a risk factor for the development of preeclampsia. By extension, increased IDO activity, reductions in IDO reactants, or increases in IDO products may represent novel therapeutic approaches for this disorder.

Original languageEnglish (US)
Article numbere12257
JournalPhysiological Reports
Volume3
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 the authors.

Keywords

  • 3-dioxygenase
  • Animal model
  • Indoleamine 2
  • Preeclampsia
  • T cell

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