The amnion is remodeled during pregnancy to protect the growing fetus it contains, and it is particularly dynamic just before and during labor. By combining ultrastructural, immunohistochemical, and Western blotting analyses, we found that human and mouse amnion membranes during labor were subject to epithelial-to-mesenchymal transition (EMT), mediated, in part, by the p38 mitogen-activated protein kinase (MAPK) pathway responding to oxidative stress. Primary human amnion epithelial cell cultures established from amnion membranes from nonlaboring, cesarean section deliveries exhibited EMT after exposure to oxidative stress, and the pregnancy maintenance hormone progesterone (P4) reversed this process. Oxidative stress or transforming growth factor-β (TGF-β) stimulated EMT in a manner that depended on TGF-β-activated kinase 1 binding protein 1 (TAB1) and p38 MAPK. P4 stimulated the reverse transition, MET, in primary human amnion mesenchymal cells (AMCs) through progesterone receptor membrane component 2 (PGRMC2) and c-MYC. Our results indicate that amnion membrane cells dynamically transition between epithelial and mesenchymal states to maintain amnion integrity and repair membrane damage, as well as in response to inflammation and mechanical damage to protect the fetus until parturition. An irreversible EMT and the accumulation of AMCs characterize the amnion membranes at parturition.

中文翻译：

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可逆的EMT和MET在妊娠和分娩期间介导羊膜重塑。

在怀孕期间对羊膜进行重塑，以保护其中包含的正在生长的胎儿，并且在分娩前和分娩过程中尤为活跃。通过结合超微结构，免疫组织化学和蛋白质印迹分析，我们发现人和小鼠羊膜在分娩过程中会经历上皮到间质转化（EMT），部分由p38促分裂原活化蛋白激酶（MAPK）介导氧化应激反应的途径。由未分娩，剖宫产的羊膜形成的主要人羊膜上皮细胞培养物在暴露于氧化应激后表现出EMT，并且维持妊娠激素黄体酮（P4）逆转了这一过程。氧化应激或转化生长因子-β（TGF-β）以依赖于TGF-β激活的激酶1结合蛋白1（TAB1）和p38 MAPK的方式刺激EMT。P4通过孕酮受体膜成分2（PGRMC2）和c-MYC刺激原代人羊膜间充质细胞（AMC）的反向转变MET。我们的结果表明，羊膜细胞在上皮和间充质状态之间动态转换，以维持羊膜完整性和修复膜损伤，以及响应炎症和机械损伤以保护胎儿直至分娩。不可分割的EMT和AMC的积累是分娩时羊膜的特征。通过孕激素受体膜成分2（PGRMC2）和c-MYC在原代人羊膜间充质细胞（AMC）中表达。我们的结果表明，羊膜细胞在上皮和间充质状态之间动态转换，以维持羊膜完整性和修复膜损伤，以及响应炎症和机械损伤以保护胎儿直至分娩。不可分割的EMT和AMC的积累是分娩时羊膜的特征。通过孕酮受体膜成分2（PGRMC2）和c-MYC在原代人羊膜间充质细胞（AMC）中表达。我们的结果表明，羊膜细胞在上皮和间充质状态之间动态转换，以维持羊膜完整性和修复膜损伤，以及响应炎症和机械损伤以保护胎儿直至分娩。不可分割的EMT和AMC的积累是分娩时羊膜的特征。