The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction

Increased fg12 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 fg12/fibroleukin gene required an fg12-knockout mouse and data on normal pattern of fg12 expression during pregnancy. Expression of fg12 protein was determined by immunostaining with specific antibody. Fg12 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 fg12 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fg12 +/-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 fg12-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fg12 +/+ X +/+ matings, but not -/- X -/- matings. Physiological expression of fg12 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fg12 expression is required for LPS to induce abortion pathology.