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|Title:||Effect of β₂‐glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody‐mediated pregnancy pathology in mice|
|Other Titles:||Effect of beta(2)-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice|
van Beijering, E.
|Citation:||Molecular Human Reproduction, 2004; 10(6):409-416|
|Publisher:||Oxford Univ Press|
|Sarah A. Robertson, Claire T. Roberts, Eline van Beijering, Katherine Pensa, Yonghua Sheng, Tong Shi, and Steven A. Krilis|
|Abstract:||ß2-Glycoprotein I (ß2GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted ß2GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional ß2GPI in pregnancy was investigated by evaluating reproductive outcomes in ß2GPI null mutant (ß2GPI–/–) mice. ß2GPI–/– mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in ß2GPI–/– mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in ß2GPI–/– implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of ß2GPI. The effect of ß2GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with ß2GPI was also explored. Two of five anti-ß2GPI antibodies induced pregnancy loss in ß2GPI+/+ mice but ß2GPI–/– mice were refractory to antibody-induced pregnancy failure. We conclude that functional ß2GPI 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 ß2GPI function and ß2GPI–immunoglobulin complex formation.|
beta 2-Glycoprotein I
|Description:||© European Society of Human Reproduction and Embryology|
|Appears in Collections:||Aurora harvest 4|
Obstetrics and Gynaecology publications
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