title: LPS-induced occult loss in mice requires FGL2.
abstract: OBJECTIVE
  FGL2 prothrombinase is required for spontaneous abortion (resorptions) in the CBA x DBA/2 model, and for abortions in C57Bl/6 (B6) mice triggered by Salmonella enteritidis lipopolysaccharide (LPS). Unlike abortions, occult losses in B6 mice, which begin before gestation day 9.5 in mice, do not require the tumor necrosis factor-alpha receptor type 1, and may be triggered by either Salmonella enteritidis or Escherichia coli LPS. Heterozygous matings of fgl2+/-xfgl2+/- B6 mice also have a high spontaneous occult loss of fgl2-/- and to a lesser extent, fgl2+/- embryos caused by hemorrhage between trophoblast and Reichert's membrane. However, the frequency of such losses appears to vary among breeding periods and between laboratories.
  
  
  METHODS
  We tested the hypothesis that FGL2-deficient embryos were uniquely susceptible to LPS by treating B6 fgl2+/-xfgl2+/- heterozygous matings with 2 microg E. coli LPS intraperitoneally on day 6.5 of pregnancy. Progesterone 2 mg in 100 microL sesame oil was administered subcutaneously at the same time to ensure that the effects of the LPS were not because of suppression of ovarian hormone production. PCR DNA genotyping was performed on embryos at day 13.5 of pregnancy, or after parturition.
  
  
  RESULTS
  Surprisingly, we found that LPS caused occult loss of fgl2+/+, and to a lesser extent fgl2+/- embryos, both at term and by PCR typing of embryos at gestation day 13.5, and these losses obscured the effect of fgl2 knockout.
  
  
  CONCLUSIONS
  Spontaneous loss of fgl2-/- embryos may relate to adhesion effects, whereas fgl2+/+ embryos are susceptible to LPS-induced loss; fgl2+/- embryos may be affected by both mechanisms. Antagonizing FGL2 could prevent occult pregnancy loss in some human and animal situations.
authors.affiliation: Toronto General Research Institute and CIHR Group on Cellular and Molecular Mechanisms of Organ Injury, Toronto Hospital, Toronto, ON, Canada.
authors.forename: Katharina
authors.initials: K
authors.lastname: Foerster
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Justin
authors.initials: J
authors.lastname: Manuel
authors.forename: Angela
authors.initials: A
authors.lastname: Bartczak
authors.forename: MingFeng
authors.initials: M
authors.lastname: Liu
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Gary A
authors.initials: GA
authors.lastname: Levy
authors.forename: David A
authors.initials: DA
authors.lastname: Clark
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics / Q000276:immunology*; D000818:Animals; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000276:immunology*; D005838:Genotype; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011247:Pregnancy
chemical_list: C490637:Fgl2 protein, mouse; D008070:Lipopolysaccharides; D005340:Fibrinogen