The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction.
Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia. Defining the physiological and pathological role of the fgl2/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2 protein was determined by immunostaining with specific antibody. Fgl2 knockout mice were generated and typed by PCR for presence of the altered gene. Immunostaining of timed CBAxDBA/2 mouse matings in a low-abortion-rate colony showed a distinct pattern of development of fgl2 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fgl2 +/-x+/- matings with a similar low abortion rate showed selective occult loss of both +/- and, to a greater extent, -/- embryos prior to gestation day 11.5, in association with haemorrhage at the anti-mesometrial pole of fgl2-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fgl2 +/+x+/+ matings, but not -/-x-/- matings. Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology.
Clark
David A
DA
Department of Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada. clarkd@mcmaster.ca
Foerster
Katharina
K
Fung
Laisum
L
He
Wei
W
Lee
Lydia
L
Mendicino
Michael
M
Markert
Udo R
UR
Gorczynski
Reginald M
RM
Marsden
Philip A
PA
Levy
Gary A
GA
D000022:Abortion, Spontaneous / Q000139:chemically induced*; D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012098:Reproduction / Q000187:drug effects; D014599:Uterus / Q000166:cytology
C490637:Fgl2 protein, mouse; D008070:Lipopolysaccharides; D005340:Fibrinogen