Differences in Cytokine Expression and STAT3 Activation between Healthy Controls and Patients of Unexplained Recurrent Spontaneous Abortion (URSA) during Early Pregnancy

Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known...

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Published inPloS one Vol. 11; no. 9; p. e0163252
Main Authors Cai, JunYing, Li, MuJun, Huang, QianYi, Fu, XiaoQian, Wu, HuiMei
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.09.2016
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Abstract Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known to involve inflammation. Here, we examine the relationship between the expression of inflammatory cytokines and the activation of downstream signaling pathways in URSA patients. Decidual and peripheral blood samples were collected from 30 URSA patients and from 30 women with normal early pregnancies. Western blot analysis was used to measure the expression levels of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), and interleukin-17 receptor(IL-17R) in the decidual samples. Enzyme-linked immunosorbent assay was used to assess the levels of IL-17, IL-10, IL-6, and IL-23 in the peripheral blood and decidual samples. In the URSA patients, the IL-10 expression levels were lower than those in the control subjects (P<0.05), whereas IL-6, IL-17, and IL-23 were all expressed at higher levels(P<0.05). Furthermore, the expression levels of IL-17R and p-STAT3 were higher in the URSA patients, exhibiting a trend similar to that of IL-23. Our finding of increased IL-23 expression in the deciduae and peripheral blood of patients with URSA suggest that this maybe a contributing factor to the pathogenesis of this disease. Likewise, STAT3 activation through its phosphorylation, which was associated with the IL-23 increase, may also be involved in URSA pathogenesis. However, the precise pathogenic mechanism requires further study.
AbstractList Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known to involve inflammation. Here, we examine the relationship between the expression of inflammatory cytokines and the activation of downstream signaling pathways in URSA patients. Decidual and peripheral blood samples were collected from 30 URSA patients and from 30 women with normal early pregnancies. Western blot analysis was used to measure the expression levels of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), and interleukin-17 receptor(IL-17R) in the decidual samples. Enzyme-linked immunosorbent assay was used to assess the levels of IL-17, IL-10, IL-6, and IL-23 in the peripheral blood and decidual samples. In the URSA patients, the IL-10 expression levels were lower than those in the control subjects (P<0.05), whereas IL-6, IL-17, and IL-23 were all expressed at higher levels(P<0.05). Furthermore, the expression levels of IL-17R and p-STAT3 were higher in the URSA patients, exhibiting a trend similar to that of IL-23. Our finding of increased IL-23 expression in the deciduae and peripheral blood of patients with URSA suggest that this maybe a contributing factor to the pathogenesis of this disease. Likewise, STAT3 activation through its phosphorylation, which was associated with the IL-23 increase, may also be involved in URSA pathogenesis. However, the precise pathogenic mechanism requires further study.
Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known to involve inflammation. Here, we examine the relationship between the expression of inflammatory cytokines and the activation of downstream signaling pathways in URSA patients. Decidual and peripheral blood samples were collected from 30 URSA patients and from 30 women with normal early pregnancies. Western blot analysis was used to measure the expression levels of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), and interleukin-17 receptor(IL-17R) in the decidual samples. Enzyme-linked immunosorbent assay was used to assess the levels of IL-17, IL-10, IL-6, and IL-23 in the peripheral blood and decidual samples. In the URSA patients, the IL-10 expression levels were lower than those in the control subjects ( P <0.05), whereas IL-6, IL-17, and IL-23 were all expressed at higher levels( P <0.05). Furthermore, the expression levels of IL-17R and p-STAT3 were higher in the URSA patients, exhibiting a trend similar to that of IL-23. Our finding of increased IL-23 expression in the deciduae and peripheral blood of patients with URSA suggest that this maybe a contributing factor to the pathogenesis of this disease. Likewise, STAT3 activation through its phosphorylation, which was associated with the IL-23 increase, may also be involved in URSA pathogenesis. However, the precise pathogenic mechanism requires further study.
Author Wu, HuiMei
Fu, XiaoQian
Huang, QianYi
Cai, JunYing
Li, MuJun
AuthorAffiliation Department of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Xavier Bichat Medical School, INSERM-CNRS—Université Paris Diderot, FRANCE
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– name: Department of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Conceptualization: MJL JYC. Data curation: MJL JYC. Formal analysis: MJL JYC. Funding acquisition: MJL. Investigation: JYC. Methodology: MJL JYC. Project administration: MJL. Resources: MJL. Software: JYC. Supervision: MJL. Visualization: JYC. Writing – original draft: JYC MJL. Writing – review & editing: MJL QYH XQF HMW.
Competing Interests: The authors have declared that no competing interests exist.
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Snippet Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be...
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StartPage e0163252
SubjectTerms Activation
Antigens
Biology and Life Sciences
Blood
Cytokines
Decidua
Enzyme-linked immunosorbent assay
Hospitals
Immune system
Immunological tolerance
Immunology
Inflammation
Interleukin
Interleukin 10
Interleukin 17
Interleukin 23
Interleukin 6
Lymphocytes
Medicine and Health Sciences
Miscarriage
Pathogenesis
Patients
Peripheral blood
Phosphorylation
Pregnancy
Research and Analysis Methods
Stat3 protein
Transcription
Transcription factors
Transducers
Womens health
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Title Differences in Cytokine Expression and STAT3 Activation between Healthy Controls and Patients of Unexplained Recurrent Spontaneous Abortion (URSA) during Early Pregnancy
URI https://www.ncbi.nlm.nih.gov/pubmed/27657728
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Volume 11
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