Molecular Human Reproduction, Vol. 10, No. 2, pp. 99-108, 2004
© European Society of Human Reproduction and Embryology 2004
The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction
1Departments of Medicine, Molecular Medicine & Pathology, Ob-Gyn, McMaster University Medical Center, Hamilton, Ontario, 2CIHR Group on Cellular and Molecular Mechanisms of Organ Injury, Toronto General Hospital Research Institute, Ontario, 3Institute of Medical Sciences, School of Graduate Studies, University of Toronto, Canada, 4Placenta-Lab, Department of Obstetrics, Friedrich Schiller University, Jena, Germany and 5Renal Division and Department of Medicine, St Michael’s Hospital, Toronto, Ontario, Canada
6 To whom correspondence should be addressed at: 1200 Main St. West Rm 3V39, Hamilton, Ontario, Canada L8N 3Z5. e-mail: clarkd{at}mcmaster.ca
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.
Key words: Key words: bacterial lipopolysaccharide/fgl2 prothrombinase/fibroleukin/haemostasis in pregnancy/spontaneous abortion
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