Work

Fibrinolytic suppression and increased uterine artery resistance are associated with embryo resorption in DBA/2 mated CBA/J mice

Year: 2026

Type: article

Abstract: Objective: This study aimed to characterize changes in prothrombotic state (hypercoagulability, hypofibrinolysis, and hemodynamic dysfunction) in DBA/2 mated CBA/J mice from embryonic day (E) 9.5 to E13.5 and to identify factors independently associated with embryo resorption and placental congestion. Method: CBA/J females were mated with DBA/2 and BALB/c males to establish the abortion-prone model and normal control, respectively. Pregnant mice were divided into normal, model, dydrogesterone (DYD), and enoxaparin sodium (ENOX) groups. Six mice per group were sacrificed at E9.5, 11.5, and 13.5. Hemodynamic parameters were assessed by Doppler ultrasound, and coagulation and fibrinolysis markers were measured in serum and placental tissues. Moreover, the univariate and multivariate regression analyses were performed to identify independently associated factors of embryo resorption and placental congestion. Results: From E9.5 to E13.5, DBA/2 mated CBA/J mice exhibited progressive hypercoagulability and fibrinolytic inhibition, with embryo resorption peaking at E13.5. On E13.5, model mice showed elevated uterine and umbilical artery resistance, decreased serum fibrinogen (FIB) and tissue-type plasminogen activator (t-PA), and elevated D-dimer and plasminogen activator inhibitor-1 (PAI-1). The placental congestion, fibrin thrombi, and collagen deposition were observed in model mice, alongside increased expression of FIB, tissue factor, and PAI-1, and reduced t-PA. DYD ameliorated embryo resorption, decreased arterial resistance and placental PAI-1. ENOX also decreased arterial resistance, but failed to rescue embryo resorption. Furthermore, multivariate regression identified uterine artery PI and RI, along with serum t-PA and PAI-1 as independently associated factors of embryo resorption, whereas uterine artery PI and RI, along with t-PA and APTT associated with placental congestion. Conclusion: DBA/2 mated CBA/J mice exhibit key hypercoagulable and hypofibrinolytic features of RPL with prothrombotic state. Uterine artery PI and RI, serum t-PA and PAI-1 may serve as potential indicators for embryo resorption and placental congestion.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1942168