Prostacyclin Assists in the Repair of Ruptured Amnions through the Proliferation and Migration of Amnion Mesenchymal Cells

Abstract

Preterm prelabor rupture of membrane (pPROM) is a risk factor for preterm birth. However, spontaneous healing of ruptured fetal membranes is occasionally clinically observed. Prostaglandins are involved in the wound-healing process in various tissues. Here, the role of prostacyclin (PGI₂) in the repair of fetal membranes was investigated in a mouse model. Ptgs1, Ptgs2, Ptgis mRNA, and PGI₂ were increased in the ruptured murine fetal membranes. Compared with the number of amnion mesenchymal cells at the intact site, the number of these cells at the rupture site was greater, and PGI₂ synthase was increased in the mesenchymal cells of the amnion. Repair of the ruptured amnion was compromised by treatment with a PGI₂ receptor (IP) antagonist, which decreased proliferation of the amnion mesenchymal cells. In contrast, an IP agonist partially restored repair of the amnion under the suppression of prostaglandin synthesis by a cyclooxygenase inhibitor. Compared with wild-type fetuses, IP-deficient fetuses exhibited impaired amnion repair, characterized by reduced proliferation of amnion mesenchymal cells observed at the rupture site. In vitro, the proliferation and migration of cultured human amnion mesenchymal cells were stimulated by an IP agonist and inhibited by an IP antagonist. These findings suggest that PGI₂ facilitates amnion repair by promoting the proliferation and migration of amnion mesenchymal cells.