title: Inflammosome in the human endometrium: further step in the evaluation of the "maternal side".
abstract: OBJECTIVE
  To investigate the expression of inflammosome components (NALP-3, associated speck-like protein containing a CARD [ASC]) and their activation (caspase-1, interleukin [IL]-1β, and IL-18 secretion) in the human endometrium from fertile and women with history of recurrent pregnancy loss (RPL).
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Ten fertile women (control group [CTR]) and 30 women with RPL.
  
  
  METHODS
  None.
  
  
  METHODS
  Endometrial samples were collected by hysteroscopy during the putative window of implantation and evaluated for chronic endometrial inflammation by hystopathological analysis. Inflammosome expression was analysed by immunohystochemical staining (27 RPL and 10 CTR women). The expression of NALP-3 and ASC protein was quantified by Western blot (30 RPL and 10 CTR women). Caspase-1 activation and IL-1β and IL-18 secretion was quantified by ELISA (30 RPL and 10 CTR women).
  
  
  RESULTS
  We observed a significantly increased expression of inflammasome NALP-3 and ASC protein, an increased activation of caspase-1, and increased levels of IL-1β and IL-18 in RPL endometrium compared with CTR.
  
  
  CONCLUSIONS
  Abnormal activation of endometrial innate immunity by means of inflammosome, stimulated by pathogen- or damage-associated molecular patterns, may represent an additional mechanism, currently not investigated, negatively interfering with endometrial receptivity. More studies are required [1] to identify the primary trigger of endometrial inflammosome activation and its clinical impact in the occurrence of RPL; and [2] to validate the inflammosome components as a novel family of endometrial biomarkers and promising therapeutic targets in RPL.
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: D'Ippolito
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tersigni
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy; International Scientific Institute Paolo VI, ISI, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marana
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Di Nicuolo
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Gaglione
authors.affiliation: Division of Anatomic Pathology and Histology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Esther Diana
authors.initials: ED
authors.lastname: Rossi
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Castellani
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy. Electronic address: nicolettadisimone@rm.unicatt.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Di Simone
mesh_terms: D000026:Abortion, Habitual / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000032:analysis; D016022:Case-Control Studies; D020170:Caspase 1 / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D010064:Embryo Implantation; D004717:Endometrium / Q000737:chemistry* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005298:Fertility; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000737:chemistry* / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis; D020382:Interleukin-18 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011247:Pregnancy
chemical_list: D015415:Biomarkers; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D018836:Inflammation Mediators; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D020170:Caspase 1
keywords: Endometrium; NALP-3; inflammosome; interleukins; miscarriage