Study on the pathogenesis of autoimmune-type recurrent spontaneous abortion by establishing a new mouse model

To establish a new mouse model for autoimmune-type recurrent spontaneous abortion (AI-RSA) and demonstrate the potential role of intrauterine immunization with β2GP-1-like antigen in AI-RSA, we performed an intrauterine injection of human β2GP-1 in BALB/c mice and unrelated protein, adjuvants, and normal saline (NS) as controls. The mean number of embryos implanted (MNEI), embryo loss rate (ELR), mean embryo bulk (MEB), and mean placental weight (MPW) were analyzed. Compared with the control mice, BALB/c mice injected with human β2GP-1 showed increased anti-β2GP-1 and MPW. Moreover, BALB/c mice immunized with human β2GP-1 exhibited hypercoagulability and vascular thrombus formation in the placenta. Electron microscopy confirmed the existence of platelet aggregation, mitochondrial swelling, and endothelial cell necrosis in the placentas of BALB/c mice immunized with human β2GP-1. These finding indicated that intrauterine immunization with β2GP-1 successfully induced AI-RSA in mice. Increased anti-β2GP-1 antibody could independently induce hypercoagulability, vascular endothelial injury, and vascular thrombus formation in the placenta, which led to AI-RSA.