Protease-activated receptor 2 contributes to placental development and fetal growth in mice

Abstract Background Protease-activated receptor 2 (PAR2) is activated by serine proteases such as coagulation tissue factor/VIIa complex, factor Xa or trypsin and is pro-angiogenic in several disease models. Impaired angiogenesis in placenta causes placental dysfunction and fetal growth restriction. PAR2 is expressed in the placenta trophoblast. However, the role of PAR2 in pregnancy remains unknown. Objective The present study aimed to examine the role of PAR2 in placental development and fetal growth using a murine model. Methods PAR2−/− or PAR2+/+ mice in the ICR background were used. Female PAR2−/− mice were mated with male PAR2−/− mice, and female PAR2+/+ mice were mated with male PAR2+/+ mice to obtain PAR2−/− and PAR2+/+ fetuses, respectively. The day a virginal plug was observed in the morning was determined as 0.5-day post-coitum (dpc). Pregnant mice were sacrificed on 13.5 or 18.5 dpc to collect samples. Results A deficiency of PAR2 significantly reduced the fetal and placental weight and impaired placental labyrinth development in mice on 18.5 dpc. Collagen IV expression in placenta labyrinth was smaller in PAR2 knockout mice compared to that of wild-type mice. A deficiency of PAR2 also reduced the expression levels of genes related to angiogenesis and coagulation in placenta. Conclusion Our data suggest that PAR2 is required for fetal growth and angiogenesis in the placenta and is thus important for a normal pregnancy.