Defective maternal-fetal interaction in a murine autoimmune model.
Anti-cardiolipin antibodies (ACA) are associated with recurrent fetal loss, but their role in this pathological condition is unknown. We recently developed an experimental mouse model of the anti-phospholipid syndrome, in which immunization of female mice with a monoclonal anti-cardiolipin antibody resulted in substantial failure of pregnancy. We observed that pre-implantation embryos derived from ACA-injected mothers exhibited morphological abnormalities and failed to implant in vitro. In the present study, we designed embryo transfer experiments to determine whether defective embryonic development originated as a maternal defect, an embryonic defect or both. Embryos (3.5 day old), taken from ACA- and control-immunized mothers were transferred into either an ACA- or a control-treated uterine environment (day 2.5 pseudopregnant females). On day 14 of gestation the incidence of pregnancy, the average number of fetuses per female and fetal resorptions were assessed. The ACA-treated uterine environment was found to be non-supportive for the development and implantation of normal embryos. Moreover, embryos derived from ACA-immunized mothers, even after their removal from the ACA-environment and transfer to a normal uterus, remained deficient. These results demonstrate that both the maternal and the embryonic compartments were defective, as a result of previous exposure to the ACA.
Tartakovsky
B
B
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Bermas
B L
BL
Sthoeger
Z
Z
Shearer
G M
GM
Mozes
E
E
D000818:Animals; D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D015551:Autoimmunity; D004195:Disease Models, Animal; D004624:Embryo Transfer; D005260:Female; D005327:Fetal Resorption / Q000276:immunology; D007116:Immunization, Passive; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal