Effect of β2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice

Sarah A. Robertson, Claire T. Roberts, Eline van Beijering, Katherine Pensa, Yonghua Sheng, Tong Shi, Steven A. Krilis

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

β2-Glycoprotein I (β2GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women. The significance of disrupted β2GPI activity in contributing to pregnancy pathology in antiphospholipid syndrome (APS) is not clear. In this study the physiological requirement for functional β2GPI in pregnancy was investigated by evaluating reproductive outcomes in β 2GPI null mutant (β2GPI-/-) mice. β 2GPI-/- mice were fertile and carried viable fetuses to term. However, there was an 18% reduction in the number of viable implantation sites in β2GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function. Placental architecture was altered in β2GPI-/- implantation sites with a 24% increase in the junctional zone: labyrinthine ratio, but placentae showed no evidence of increased thrombosis in the absence of β2GPI. The effect of β2GPI genotype on pregnancy success after passive transfer of human and mouse antibodies reactive with β 2GPI was also explored. Two of five anti-β 2GPI antibodies induced pregnancy loss in β 2GPI+/+ mice but β2GPI-/- mice were refractory to antibody-induced pregnancy failure. We conclude that functional β2GPI 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 β2GPI function and β 2GPI-immunoglobulin complex formation.

Original languageEnglish
Pages (from-to)409-416
Number of pages8
JournalMolecular Human Reproduction
Volume10
Issue number6
DOIs
Publication statusPublished - 1 Jun 2004
Externally publishedYes

Keywords

  • β-glycoprotein I
  • Antiphospholipid
  • Autoantibodies
  • Placenta
  • Pregnancy

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