Molecular Human Reproduction, Vol. 7, No. 2, 185-194,
February 2001
© 2001 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2
1 Department of Medicine, Pathology & Molecular Medicine, and Department of Obstetrics & Gynecology, McMaster University, 1200 Main St West, Room 3V39, Hamilton, Ontario, Canada L8N 3Z5, and 2 CIHR Group on Mechanisms of Organ Injury, Toronto Hospital, University of Toronto, Toronto, Ontario, Canada
Abstract
Spontaneous abortion of normal karyotype embryos in mice and in humans is associated with an increase in uterine T helper (Th) 1 type proinflammatory cytokines, tumour necrosis factor (TNF)-
, interferon-
and interleukin (IL)-1, and a deficiency of Th2/3 type cytokines, IL-4, IL-10, and transforming growth factor (TGF)-ß2. In mice, Th1 cytokines up-regulate a novel prothrombinase, fgl2, which via thrombin, leads to activation of polymorphonuclear leukocytes that terminate the pregnancy. Here we show that Th1 cytokines up-regulate fgl2 mRNA in fetal trophoblast and secondary decidua of CBA/JxDBA/2 and CBA/JxBALB/c matings, and promote fibrin deposition. This pattern is accompanied by a high rate of abortion. However, the spontaneous abortion rates in abortion-prone CBAxDBA/2 matings and in low abortion rate CBAxBALB/c matings were significantly lower than that expected from the frequency of implantations with high levels of fibrin and fgl2 mRNAhi. As the glycoprotein OX-2 occurs in the pregnant rat uterus and can deviate cytokine responses to Th2/3, we investigated OX-2 in pregnant CBA/J mice. We found OX-2 mRNA was present at the same sites as fgl2 mRNA, but was reduced in response to Th1 cytokines. Furthermore, anti-OX-2 raised the abortion rate to predicted levels, while recombinant OX-2 dramatically reduced the abortion rate. Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto–maternal interface.
abortion/Fgl2 prothrombinase/mouse embryo/OX-2
Notes
3 To whom correspondence should be addressed. E-mail: clarkd{at}fhs.McMaster.ca
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