title: Down-regulation of S100A11, a calcium-binding protein, in human endometrium may cause reproductive failure.
abstract: BACKGROUND
  Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses.
  
  
  OBJECTIVE
  The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation.
  
  
  METHODS
  S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA.
  
  
  RESULTS
  S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11.
  
  
  CONCLUSIONS
  Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive failure.
authors.affiliation: Department of Reproductive Endocrinology, Zhejiang Women's Hospital, and Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310006, China.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Liu
authors.forename: Guo-Lian
authors.initials: GL
authors.lastname: Ding
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Pan
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wang
authors.forename: Run-Ju
authors.initials: RJ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Shu
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000328:Adult; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002822:Choriocarcinoma; D015536:Down-Regulation / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007247:Infertility, Female / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000503:physiopathology*; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism*; D014594:Uterine Neoplasms
chemical_list: D002135:Calcium-Binding Proteins; D009418:S100 Proteins; C531047:S100A11 protein, mouse; C072337:S100A11 protein, human