Immunology: Defective maternal--fetal interaction in a murine autoimmune model

Anti-cardiolipin antibodies (ACA) are associated with recurrentfetal loss, but their role in this pathological condition isunknown. We recently developed an experimental mouse model ofthe anti-phospholipid syndrome, in which immunization of femalemice with a monoclonal anti-cardiolipin antibody resulted insubstantial failure of pregnancy. We observed that pre-implantationembryos derived from ACA-injected mothers exhibited morphologicalabnormalities and failed to implant in vitro. In the presentstudy, we designed embryo transfer experiments to determinewhether defective embryonic development originated as a maternaldefect, an embryonic defect or both. Embryos (3.5 day old),taken from ACA- and control-immunized mothers were transferredinto either an ACA-or a control-treated uterine environment(day 2.5 pseudo-pregnant females). On day 14 of gestation theincidence of pregnancy, the average number of fetuses per femaleand fetal resorptions were assessed. The ACA-treated uterineenvironment was found to be non-supportive for the developmentand implantation of normal embryos. Moreover, embryos derivedfrom ACA-immunized mothers, even after their removal from theACA-environment and transfer to a normal uterus, remained deficientThese results demonstrate that both the maternal and the embryoniccompartments were defective, as a result of previous exposureto the ACA.