You Yilan, Qian Zhiwen, Jiang Ying, Chen Lingyan, Wu Danping, Liu Lu, Zhang Feng, Ning Xin, Zhang Yan, Xiao Jianping
Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, China.
Front Cell Dev Biol. 2024 Nov 12;12:1482838. doi: 10.3389/fcell.2024.1482838. eCollection 2024.
Ferroptosis, a distinct form of non-apoptotic cell death characterized by iron dependency and lipid peroxidation, is increasingly linked to various pathological conditions in pregnancy and liver diseases. It plays a critical role throughout pregnancy, influencing processes such as embryogenesis, implantation, and the maintenance of gestation. A growing body of evidence indicates that disruptions in these processes can precipitate pregnancy-related disorders, including pre-eclampsia (PE), gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP). Notably, while ICP is primarily associated with elevated maternal serum bile acid levels, its precise etiology remains elusive. Oxidative stress induced by bile acid accumulation is believed to be a significant factor in ICP pathogenesis. Similarly, the liver's susceptibility to oxidative damage underscores the importance of lipid metabolism dysregulation and impaired iron homeostasis in the progression of liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cholestatic liver injury, autoimmune hepatitis (AIH), acute liver injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). This review discusses the shared signaling mechanisms of ferroptosis in gestational and hepatic diseases, and explores recent advances in understanding the mechanisms of ferroptosis and its potential role in the pathogenesis of gestational and hepatic disorders, with the aim of identifying viable therapeutic targets.
铁死亡是一种独特的非凋亡性细胞死亡形式，其特征为铁依赖性和脂质过氧化，越来越多地与妊娠和肝脏疾病中的各种病理状况相关联。它在整个孕期发挥着关键作用，影响着胚胎发生、着床和妊娠维持等过程。越来越多的证据表明，这些过程的紊乱会引发与妊娠相关的疾病，包括子痫前期（PE）、妊娠期糖尿病（GDM）和妊娠肝内胆汁淤积症（ICP）。值得注意的是，虽然ICP主要与母体血清胆汁酸水平升高有关，但其确切病因仍不清楚。胆汁酸积累诱导的氧化应激被认为是ICP发病机制中的一个重要因素。同样，肝脏对氧化损伤的易感性突出了脂质代谢失调和铁稳态受损在酒精性肝病（ALD）、非酒精性脂肪性肝病（NAFLD）、胆汁淤积性肝损伤、自身免疫性肝炎（AIH）、急性肝损伤、病毒性肝炎、肝纤维化和肝细胞癌（HCC）等肝脏疾病进展中的重要性。本综述讨论了妊娠和肝脏疾病中铁死亡的共同信号机制，并探讨了在理解铁死亡机制及其在妊娠和肝脏疾病发病机制中的潜在作用方面的最新进展，旨在确定可行的治疗靶点。
