Mol. Hum. Reprod. Advance Access published online on April 20, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah058
© 2004 by Oxford University Press
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1 Department of Obstetrics and Gynaecology and Reproductive Medicine Unit, University of Adelaide, Adelaide, SA 5005, Australia
* To whom correspondence should be addressed. E-mail: sarah.robertson{at}adelaide.edu.au.
Revised March 15, 2004
Accepted March 21, 2004
Article
Effect of
2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice
2 Department of Immunology, Allergy and Infectious Disease and Department of Medicine, University of New South Wales, St George Hospital, NSW 2217, Australia
Abstract 
2-Glycoprotein I (2GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted 2GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional 2GPI in pregnancy was investigated by evaluating reproductive outcomes in 2GPI null mutant (2GPI-/-) mice. 2GPI-/- mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in 2GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in 2GPI-/- implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of 2GPI. The effect of 2GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with 2GPI was also explored. Two of five anti-2GPI antibodies induced pregnancy loss in 2GPI+/+ mice but 2GPI-/- mice were refractory to antibody-induced pregnancy failure. We conclude that functional 2GPI is not essential for successful pregnancy in mice, but optimal placental development and fetal growth require this molecule. Together these data are consistent with pathogenic mechanisms in antiphospholipid syndrome involving both neutralization of 2GPI function and 2GPI-immunoglobulin complex formation.2-glycoprotein I/placenta/pregnancy
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