The Cecil H. and Ida Green Center for Reproductive Biological Sciences, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Sci Rep. 2017 Oct 13;7(1):13139. doi: 10.1038/s41598-017-13296-1.
Preterm premature rupture of membrane (pPROM) is associated with 30-40% of preterm births. Infection is considered a leading cause of pPROM due to increased levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are positive for microbial organisms by amniotic fluid culture. Interestingly, in some pregnancies complicated by preterm premature rupture of membranes (pPROM), membranes heal spontaneously and pregnancy continues until term. Here, we investigated mechanisms of amnion healing. Using a preclinical mouse model, we found that small ruptures of the fetal membrane closed within 72 h whereas healing of large ruptures was only 40%. Small rupture induced transient upregulation of cytokines whereas large ruptures elicited sustained upregulation of proinflammatory cytokines in the fetal membranes. Fetal macrophages from amniotic fluid were recruited to the wounded amnion where macrophage adhesion molecules were highly expressed. Recruited macrophages released limited and well-localized amounts of IL-1β and TNF which facilitated epithelial-mesenchymal transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated within 24 h. Migration and healing of the amnion mesenchymal compartment, however, remained compromised. These findings provide novel insights regarding unique healing mechanisms of amnion.
早产胎膜早破（pPROM）与 30-40%的早产有关。由于羊水内促炎细胞因子水平升高，感染被认为是 pPROM 的主要原因。然而，只有 30%的羊水培养呈微生物阳性。有趣的是，在一些由早产胎膜早破（pPROM）引起的妊娠中，胎膜会自发愈合，妊娠会持续到足月。在这里，我们研究了羊膜愈合的机制。使用临床前小鼠模型，我们发现胎儿膜的小破裂会在 72 小时内闭合，而大破裂的愈合仅为 40%。小破裂会引起细胞因子的短暂上调，而大破裂会引起胎儿膜中促炎细胞因子的持续上调。羊水来源的胎儿巨噬细胞被募集到受伤的羊膜中，在那里巨噬细胞黏附分子高度表达。募集的巨噬细胞释放有限且局部定位的 IL-1β 和 TNF，这有助于上皮-间充质转化（EMT）和上皮细胞迁移。Arg1+巨噬细胞在 24 小时内占主导地位。然而，羊膜间充质区的迁移和愈合仍然受损。这些发现为羊膜的独特愈合机制提供了新的见解。
