title: Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration.
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 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.
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zong
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Luo
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Jia
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Gynaecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Minghong
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Gynaecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Bao
authors.affiliation: Department of Obstetrics and Gynaecology, Punan hospital, Shanghai, 2000125, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D020780:Matrix Metalloproteinase 9
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