title: Human chorionic gonadotropin potentially affects pregnancy outcome in women with recurrent implantation failure by regulating the homing preference of regulatory T cells.
abstract: OBJECTIVE
  Human chorionic gonadotropin (hCG) and regulatory T cells (Tregs) have been suggested to play important roles during the initial stage of pregnancy. However, the clinical relevance and mechanism of the effects of hCG on Treg functions in women with recurrent implantation failure (RIF) remain to be elucidated.
  
  
  METHODS
  Thirty-four RIF and twenty-three control women were included in the study. Endometrial and peripheral Tregs were analyzed by immunohistochemistry and flow cytometry, respectively. Tregs were generated from naïve CD4+T cells by stimulation with anti-CD3/CD28 in the presence or absence of hCG, and the subsets were analyzed by flow cytometry, Western blotting, and qPCR.
  
  
  RESULTS
  The percentages of endometrial FOXP3+Tregs and peripheral CCR4+FOXP3+Tregs were significantly lower in the women with RIF than in the healthy controls. In addition, the percentages of CCR4+FOXP3+Tregs and TGF-β-expressing FOXP3+Tregs were increased following the stimulation of naïve CD4+T cells with anti-CD3/CD28, and these increases were concomitant with AKT and ERK dephosphorylation.
  
  
  CONCLUSIONS
  The results of this study provide novel evidence supporting a role of hCG in regulating the differentiation of peripheral FOXP3+Tregs. The alterations of circulating Tregs may positively affect the pregnancy outcomes of patients with a history of RIF.
authors.affiliation: Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China.|Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Liang-Hui
authors.initials: LH
authors.lastname: Diao
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Guan-Gui
authors.initials: GG
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.|Key Laboratory in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
authors.forename: Yuan-Chang
authors.initials: YC
authors.lastname: Zhu
authors.affiliation: Laboratory for Translational Immunology, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Tu
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.|Laboratory for Translational Immunology, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Ruo-Chun
authors.initials: RC
authors.lastname: Lian
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000293:Adolescent; D000328:Adult; D002465:Cell Movement; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D010064:Embryo Implantation; D004717:Endometrium / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000276:immunology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D054398:Receptors, CCR4 / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: C515354:CCR4 protein, human; D006063:Chorionic Gonadotropin; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054398:Receptors, CCR4; D011974:Receptors, LH; D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta
keywords: chemokine-chemokine receptor; endometrial receptivity; human chorionic gonadotropin; recurrent implantation failure; regulatory T cells