Embryonic and Placental Damage Induced by Maternal Autoimmune Diseases - What Can We Learn from Experimental Models

Abstract

Systemic Lupus Erythematosus 186 antibodies are typically found among the patients. Complement activation was shown to play a role in antiphospholipid antibody-mediated fetal loss associated with inflammatory process, when C4d, a degradation product of C4 was demonstrated in human placenta of SLE patients (Cohen et al., 2011), as well as diminished number of T regulatory cells, associated with pregnancy loss and pre-eclampsia (Tower et al., 2011). Circulating microparticles that expose phospholipids in the outer membrane and induce coagulation via tissue factor have been associated with lupus anticoagulants and poor obstetric outcome (Alijotas-Reig et al., 2009). Other reports indicate that enhanced oxidative stress could be linked to autoimmune diseases; however, there is lack of data about anti oxidant status of the placenta and embryos during pregnancy in women suffering from autoimmune diseases. 2. The role of experimental animal studies in evaluation of pregnancy complications among women suffering from autoimmune diseases As more than one mechanism of pathogenesis exists for fetal damage in autoimmune diseases, experimental animal models can be used to isolate the different causative effects. Evaluation of the role of different antibodies and molecules can be obtained by direct injection or induction of antibodies production in the pregnant animals and evaluation of the resultant effect on the embryos and fetuses. In such case the effect is evaluated in normal animals rather than being secondary to an autoimmune disease. Previous published studies revealed fetal damage induced by various antibodies. A smaller litter size was demonstrated after the injection to pregnant BALB/C mice with a human cytomegalovirus-peptide-induced monoclonal antiphospholipid (Gharavi et al., 2004). Fetal heart block and bradycardia were evidenced in a murine model as a result of maternal autoantibodies to Ro and La antigen induced by maternal immunization (Suzuki et al., 2005). In addition maternal immunization with DNA memitope in mice led to the induction of autoantibodies that bind DNA and the N-methyl-D-aspartate receptor in the maternal circulation leading to increased neocortical cell death in the fetal brain and subsequent delayed acquisition of neonatal reflexes and cognitive impairments in the adult offspring. In this model the antibodies that were detected in the fetal neocortex outside of blood vessels evidenced their transport through fetal circulation until binding to the fetal brain (Lee et al., 2009). We previously found that the immunization of BALB /C mice with mouse laminin-1 was followed by the development of anti-laminin-1 antibodies. A double fetal resorption rate and lower fetal and placental weight was found in the laminin-1 immunized group compared with controls. Resorption rate was highest in the subgroup of animals with very high levels of anti-laminin-1 (Matalon et al., 2003). Other molecules were also found to have direct embryotoxic effects. The injection of a low-molecular weight fraction of boiled h...