Abstract：
Aims: Preterm birth (PTB), recognized as delivery before 37 weeks of gestation, is a multifactorial syndrome characterizing as the main cause of neonatal mortality. Reactive oxygen species (ROS) have been identified as proinflammatory factors to cause placental inflammation, thereby resulting in several pregnancy outcomes. To date, limited knowledge regarding the underlying mechanisms of ROS-induced PTB has been reported. In this study, we aimed to investigate the role of oxidative stress in PTB and the protective effects of mitochondria-targeted antioxidant MitoTEMPO (MT) on preterm labor and offspring mice. Results: In this study, we found that preterm placentas had abnormal mitochondrial function, oxidative stress, and inflammatory response. In the lipopolysaccharide (LPS)-induced PTB mouse model, MT inhibited PTB by ameliorating maternal oxidative stress and inflammation, especially in placentas, thus improving placental function to maintain pregnancy. Antenatal administration of MT prevented LPS-induced fetal brain damage in acute phase and improved long-term neurodevelopmental impairments. Furthermore, our in vitro investigations validated that MT retarded the ROS accumulation and inflammatory response in LPS-stimulated trophoblast cells by promoting Kelch-like ECH-associated protein 1 (Keap1) degradation and subsequently activating nuclear factor erythroid 2-related factor 2 (Nrf2). By inhibiting Nrf2 activation, we discovered that the anti-inflammation and protective characteristics of MT were Nrf2/ARE pathway dependent. Innovation and Conclusion: MT inhibited PTB and fetal brain injury by inhibiting maternal inflammation and improving placental function through Keap1/Nrf2/antioxidant response element signaling pathway. Our findings provide a novel therapeutic strategy for PTB.
摘要：
目的：早产，在妊娠37周前被确认为分娩，是一种多因素综合征，是新生儿死亡的主要原因。活性氧（ROS）已被确定为导致胎盘炎症的炎症因子，从而导致几种妊娠结局。迄今为止,关于ROS诱导早产的潜在机制的知识有限。这里,我们旨在研究氧化应激在早产中的作用,以及线粒体靶向抗氧化剂MitoTEMPO(MT)对早产和子代小鼠的保护作用.
结果：这里，我们发现早产胎盘线粒体功能异常,氧化应激和炎症反应。在LPS诱导的早产小鼠模型中,MT通过改善母体氧化应激和炎症抑制早产，尤其是胎盘,从而改善胎盘功能维持妊娠。产前给予MT可预防LPS引起的急性期胎儿脑损伤，并改善长期神经发育障碍。此外，我们的体外研究证实，MT通过促进Keap1降解并随后激活Nrf2来延缓LPS刺激的滋养细胞中的ROS积累和炎症反应。通过抑制Nrf2激活，我们发现MT的抗炎和保护特性是Nrf2/ARE通路依赖性的.
结论：MT通过Keap1/Nrf2/ARE信号通路抑制母体炎症和改善胎盘功能，从而抑制早产和胎儿脑损伤。我们的发现为早产提供了一种新的治疗策略。
结果：这里，我们发现早产胎盘线粒体功能异常,氧化应激和炎症反应。在LPS诱导的早产小鼠模型中,MT通过改善母体氧化应激和炎症抑制早产，尤其是胎盘,从而改善胎盘功能维持妊娠。产前给予MT可预防LPS引起的急性期胎儿脑损伤，并改善长期神经发育障碍。此外，我们的体外研究证实，MT通过促进Keap1降解并随后激活Nrf2来延缓LPS刺激的滋养细胞中的ROS积累和炎症反应。通过抑制Nrf2激活，我们发现MT的抗炎和保护特性是Nrf2/ARE通路依赖性的.
结论：MT通过Keap1/Nrf2/ARE信号通路抑制母体炎症和改善胎盘功能，从而抑制早产和胎儿脑损伤。我们的发现为早产提供了一种新的治疗策略。
