A unique preliminary study on placental apoptosis in mice with passive immunization of anti-phosphatidylethanolamine antibodies and anti-factor XII antibodies

Am J Reprod Immunol. 2011 Nov;66(5):373-84. doi: 10.1111/j.1600-0897.2011.01008.x. Epub 2011 May 27.

Abstract

Problem: Antiphospholipid antibodies have been investigated both in humans and in animal models. In contrast, there are fewer reports describing anti-phosphatidylethanolamine (aPE) antibodies in humans, and there are no reports of animal studies with aPE till date. Clinically, FXII deficiency or anti-FXII antibodies are sometimes associated with aPE in patients with recurrent pregnancy loss. Therefore, we asked whether aPE and/or anti-FXII in mice could cause fetal resorption, placental thrombosis and apoptosis. Moreover, antibodies to respective target antigens (LDC27 or IPP30) could cause pregnancy failure as well.

Methods of study: Animal models were used to carry out these objectives. All the animals were immunized with different antibodies by passive immunization. Placental samples were used for various observations.

Results and conclusions: Mice with passive immunization of aPE (or anti-LDC27) and aFXII (or anti-IPP30) produced a slight increase in fetal resorption, but markedly induced thrombosis and hemorrhage in the placenta associated with lower platelet counts and increased placental apoptosis. In addition, fewer mitotic cells, less trophoblast giant cell invasion, and more shrunken cells in the deciduas were seen. Our study supports the pathogenic role of aPE and aFXII in pregnancy complications and also suggests a beneficial role of LDC27 and IPP30 antigens on pregnancy failures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Induced
  • Animals
  • Antibodies, Antiphospholipid / administration & dosage
  • Antibodies, Antiphospholipid / adverse effects*
  • Antibodies, Antiphospholipid / immunology
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Factor XII / immunology*
  • Female
  • Fetal Resorption / etiology*
  • Humans
  • Immunization, Passive / adverse effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Phosphatidylethanolamines / immunology
  • Placenta / drug effects
  • Placenta / immunology
  • Placenta / pathology*
  • Placenta Diseases / etiology
  • Placenta Diseases / physiopathology
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / pathology
  • Thrombosis / complications

Substances

  • Antibodies, Antiphospholipid
  • Antibodies, Monoclonal
  • Phosphatidylethanolamines
  • Factor XII