title: The Role of C5a Receptor Signaling in Endotoxin-Induced Miscarriage and Preterm Birth.
abstract: OBJECTIVE
  Complement factor 5a (C5a), a potent pro-inflammatory mediator of the complement system, has been implicated in fetal rejection throughout gestation, from miscarriage to preterm birth. This study aimed to investigate the role of the principal C5a receptor, C5aR1 (CD88), in both miscarriage and preterm birth, in a bacterial endotoxin (lipopolysaccharide; LPS) murine model.
  
  
  METHODS
  Wild-type and C5ar1 knockout mice were administered LPS at 9.5 or 15.5 days post-conception to induce miscarriage or preterm birth, respectively.
  
  
  RESULTS
  C5ar1 knockout mice were protected against miscarriage in response to administration of LPS in early gestation. However, the absence of C5aR1 had no effect on the rates of preterm birth when LPS was administered in late gestation.
  
  
  CONCLUSIONS
  There may be a gestational window in which excessive activation of C5a can exert deleterious effects in pregnancy. Future strategies targeting the C5a-C5aR1 signaling axis should be considered to ameliorate miscarriages in patients with recurrent pregnancy loss.
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.|School of Medicine, University of Queensland, Brisbane, Qld, Australia.
authors.forename: Kerina J
authors.initials: KJ
authors.lastname: Denny
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.
authors.forename: Liam G
authors.initials: LG
authors.lastname: Coulthard
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.
authors.forename: Susanna
authors.initials: S
authors.lastname: Mantovani
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Simmons
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Taylor
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Qld, Australia.
authors.forename: Trent M
authors.initials: TM
authors.lastname: Woodruff
mesh_terms: D000034:Abortion, Veterinary / Q000276:immunology*; D000818:Animals; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D044087:Receptor, Anaphylatoxin C5a
keywords: Complement; complement factor 5a; inflammation; miscarriage; pregnancy; preterm birth