Protease-activated receptor-1 expression in cytotrophoblasts and platelet-fibrin thrombus formation increase in placenta accreta spectrum

Abstract Background Placenta accreta spectrum (PAS) is characterized by abnormal trophoblastic invasion into the uterine myometrium and is a cause of postpartum hemorrhage and maternal death. Protease-activated receptor-1 (PAR-1) promotes various cellular actions, including invasion. Here, we analyzed the expression of PAR-1, platelet antigen, and fibrin in PAS. Methods We analyzed 49 PAS cases (placenta accreta vera [accreta vera], 31 cases; placenta increta [increta], 8 cases; placenta percreta [percreta], 10 cases, classified by the degree of placental villous invasion) and 33 control cases. We immunohistochemically examined the expression of PAR-1, platelet glycoprotein (GP) IIb/IIIa, and fibrin. Results The frequency of previous cesarean section was higher in the increta and percreta groups than in the control and accreta vera groups. PAR-1 expression in placental villi was weak and limited in extent in control cases, whereas immunoreactivity and staining density increased in increta and percreta. Immunofluorescence revealed PAR-1 expression in cytotrophoblasts of placental villi and in aggregated platelets. PAR-1 expression scores in cytotrophoblasts increased significantly with the degree of villous invasion (accreta vera, increta, percreta) compared with controls. The immunopositive areas for GPIIb/IIIa and fibrin were significantly larger in PAS groups than in controls. Furthermore, the immunopositive areas for platelets and fibrin were positively correlated with the PAR-1 expression score. Conclusion These results indicate that PAR-1 may play a role in placental villous invasion and that a thrombogenic placental environment may influence PAR-1 activation.