LAUSR

The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the repair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cultured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor–β (TGF-β)–Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells. Description Repairs to ruptures in the amniotic sac may involve EMT elicited by fetal macrophages. Fetal macrophages to the rescue Premature rupture of the amniotic sac, which encloses the fetus, may trigger preterm birth. Because the amniotic sac may reseal, Kawamura et al. investigated repair mechanisms in the innermost epithelial cell layer of the amniotic sac, known as the amnion. The authors found that macrophages were recruited to rupture sites in human and mouse amnion, which showed signs of epithelial-mesenchymal transition (EMT), a process that confers mesenchymal attributes to epithelial cells and that is critical for tissue repair. Depletion of macrophages in fetuses in pregnant mice prevented macrophage recruitment, EMT, and repair of amnion ruptures. Thus, fetal macrophages induce EMT in the epithelial cells surrounding rupture sites in the amnion to facilitate repair.