Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration

Scientific Reports
Shanshan ZongQian Zhou

Abstract

In pregnancy, trophoblast proliferation, migration and invasion are important for the establishment and maintenance of a successful pregnancy. Impaired trophoblast function has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy, but the underlying mechanisms remain unclear. Indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan along the kynurenine pathway, is highly expressed in the placenta and serum during pregnancy. Here, we identified a novel function of IDO in regulating trophoblast cell proliferation and migration. We showed that IDO expression and activity were decreased in unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancy. Furthermore, blocking IDO in human trophoblast cells led to reduced proliferation and migration, along with decreased STAT3 phosphorylation and MMP9 expression. Increased STAT3 phosphorylation reversed the IDO knockdown-suppressed trophoblast cell proliferation and migration. In addition, the overexpression of IDO promoted cell proliferation and migration, which could be abolished by the STAT3 signaling inhibitor (AG490). Finally, we observed similar reductions of STAT3 phosphorylation and MMP9 expression in URSA p...Continue Reading

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Citations

Jul 19, 2016·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Chutima RoomruangwongMichael Maes
Jul 25, 2017·International Journal of Molecular Sciences·Kang XuYulong Yin
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Jul 20, 2019·International Journal of Tryptophan Research : IJTR·Adrian C Williams, Lisa J Hill
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May 23, 2017·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Zhiyan XuFengnian Rong
Jan 10, 2021·Journal of Reproductive Immunology·Shao-Liang YangMing-Qing Li
Jan 8, 2021·Immunopharmacology and Immunotoxicology·Yinghua LiLili Huang
Jan 30, 2021·BMC Veterinary Research·Natsumi FuneshimaKoumei Shirasuna
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Mar 16, 2021·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Clement Adu-GyamfiMelinda Suchard

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Methods Mentioned

BETA
RSA
PCR
Protein Assay
Assay

Software Mentioned

Image J
Metamorph

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