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Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration
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 r...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728682/ https://www.ncbi.nlm.nih.gov/pubmed/26814137 http://dx.doi.org/10.1038/srep19916 |
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author | Zong, Shanshan Li, Chunqing Luo, Chengfeng Zhao, Xin Liu, Chunhong Wang, Kai Jia, Wenwen Bai, Mingliang Yin, Minghong Bao, Shihua Guo, Jie Kang, jiuhong Duan, Tao Zhou, Qian |
author_facet | Zong, Shanshan Li, Chunqing Luo, Chengfeng Zhao, Xin Liu, Chunhong Wang, Kai Jia, Wenwen Bai, Mingliang Yin, Minghong Bao, Shihua Guo, Jie Kang, jiuhong Duan, Tao Zhou, Qian |
author_sort | Zong, Shanshan |
collection | PubMed |
description | 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 patients. These results indicate that the level of IDO expression may be associated with pregnancy-related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway. |
format | Online Article Text |
id | pubmed-4728682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47286822016-02-01 Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration Zong, Shanshan Li, Chunqing Luo, Chengfeng Zhao, Xin Liu, Chunhong Wang, Kai Jia, Wenwen Bai, Mingliang Yin, Minghong Bao, Shihua Guo, Jie Kang, jiuhong Duan, Tao Zhou, Qian Sci Rep Article 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 patients. These results indicate that the level of IDO expression may be associated with pregnancy-related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway. Nature Publishing Group 2016-01-27 /pmc/articles/PMC4728682/ /pubmed/26814137 http://dx.doi.org/10.1038/srep19916 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zong, Shanshan Li, Chunqing Luo, Chengfeng Zhao, Xin Liu, Chunhong Wang, Kai Jia, Wenwen Bai, Mingliang Yin, Minghong Bao, Shihua Guo, Jie Kang, jiuhong Duan, Tao Zhou, Qian Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title | Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title_full | Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title_fullStr | Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title_full_unstemmed | Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title_short | Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
title_sort | dysregulated expression of ido may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728682/ https://www.ncbi.nlm.nih.gov/pubmed/26814137 http://dx.doi.org/10.1038/srep19916 |
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