title: Modulation of tumor necrosis factor-stimulated gene-6 (TSG-6) expression in human endometrium.
abstract: BACKGROUND
  The human endometrium undergoes repetitive, cyclical changes under the influence of endocrine signals (estrogen and progesterone). In particular, the extensive tissue remodeling, angiogenesis and leukocyte infiltration that occur during decidualization of the endometrium give rise to an environment that is permissive to blastocyst attachment. However, it is now well established that crosstalk (via paracrine signals) between the trophoblast and the endometrium is also a key for successful implantation. Microarray studies have identified TSG-6 as a gene with elevated expression in endometrial stromal cells following the exposure to trophoblast and immune cell products. TSG-6 is an inflammation-associated protein which acts as a potent inhibitor of neutrophil extravasation and also plays important roles in matrix remodeling, e.g., by promoting hyaluronan (HA) cross-linking and down-regulating the protease network. Female TSG-6 (-/-) mice are infertile and this has been attributed to their inability to ovulate; however, the importance of TSG-6 in implantation has not been directly investigated.
  
  
  METHODS
  Real-time PCR, as well as immunofluorescence staining was performed on endometrial biopsies of proliferative and secretory phase samples. In addition stromal cell cultures of human endometrium were used to assess the influence of different stimulating factors on the TSG-6 gene and protein expression via real-time PCR and ELISA.
  
  
  RESULTS
  Herein demonstrate that TSG-6 mRNA is expressed by the endometrium during the proliferative and secretory phases of the menstrual cycle. We also show that conditioned media from placental tissues induce rapid upregulation of TSG-6 mRNA expression and sustained protein secretion, with evidence that TNF is an important factor in this effect. Furthermore, we demonstrate changes in protein expression in the mid-secretory phase in women affected by recurrent abortions.
  
  
  CONCLUSIONS
  These data suggest that TSG-6 expression might be essential in endometrial matrix organization and feto-maternal communication during the implantation process.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, INF440, 69120, Heidelberg, Germany.
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Milner
authors.forename: Joanna
authors.initials: J
authors.lastname: Williams
authors.forename: Lena
authors.initials: L
authors.lastname: Hauck
authors.forename: Julia
authors.initials: J
authors.lastname: Jauckus
authors.forename: Thomas
authors.initials: T
authors.lastname: Strowitzki
authors.forename: Ariane
authors.initials: A
authors.lastname: Germeyer
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005498:Follicular Phase / Q000378:metabolism; D006801:Humans; D008183:Luteal Phase / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; C072273:TNFAIP6 protein, human