title: Human trophectoderm apposition is regulated by interferon γ-induced protein 10 (IP-10) during early implantation.
abstract: BACKGROUND
  The first step in human implantation is the attraction of the blastocyst to the endometrium. We aimed to study attraction of the human blastocyst to the endometrium, and how this process is accomplished by chemokines secreted by the endometrium.
  
  
  METHODS
  Blastocyst trophectoderm cells and other trophoblast lineage cells were subjected to attraction assays by IP-10 and other chemokines using transwell migration and chemotaxis assays. Chemokine expression and secretion were investigated using immunohistochemistry, ELISA, FACS analysis, and RT-PCR on material from flushing of the uterine cavity in endometrial biopsies. Chemokine receptor expression by blastocyst trophectoderm following PGD biopsy, trophectoderm derived from hES, placental villi, and other trophoblast lineage cells were characterized by the same methods.
  
  
  RESULTS
  IP-10 dramatically attracted trophectoderm derived from hES cells and other lineages by interaction with CXCR3 chemokine receptors, as shown by both chemotaxis and transwell migration. High levels of IP-10 were detected throughout the menstrual cycle at flushing of the uterine cavity. Immunohistochemistry, FACS analysis, and RT-PCR of endometrial biopsy detected IP-10 in glandular and stromal cells of the endometrium. High levels of IP-10 were detected in condition medium of the endometrial stromal and glandular cells. Of all of the chemokine/chemokine receptor combinations examined, the IP-10/CXCR3 interaction was the only cytokine that was significantly elevated.
  
  
  CONCLUSIONS
  While they await the wandering blastocyst, IP-10 is produced by many cells of the endometrium, but not by endometrial natural killer cells.
  
  
  CONCLUSIONS
  Endometrial IP-10 may specifically attract human blastocyst trophectoderm cells early in implantation.
authors.affiliation: Division of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: H Y
authors.initials: HY
authors.lastname: Sela
authors.forename: D S
authors.initials: DS
authors.lastname: Goldman-Wohl
authors.forename: R
authors.initials: R
authors.lastname: Haimov-Kochman
authors.forename: C
authors.initials: C
authors.lastname: Greenfield
authors.forename: S
authors.initials: S
authors.lastname: Natanson-Yaron
authors.forename: Y
authors.initials: Y
authors.lastname: Hamani
authors.forename: A
authors.initials: A
authors.lastname: Revel
authors.forename: Y
authors.initials: Y
authors.lastname: Lavy
authors.forename: O
authors.initials: O
authors.lastname: Singer
authors.forename: N
authors.initials: N
authors.lastname: Yachimovich-Cohen
authors.forename: T
authors.initials: T
authors.lastname: Turetsky
authors.forename: O
authors.initials: O
authors.lastname: Mandelboim
authors.forename: B
authors.initials: B
authors.lastname: Reubinoff
authors.forename: S
authors.initials: S
authors.lastname: Yagel
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D002824:Chorionic Villi / Q000502:physiology; D046508:Culture Techniques; D004475:Ectoderm / Q000187:drug effects* / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3