Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
J Cell Mol Med. 2022 May;26(10):2947-2958. doi: 10.1111/jcmm.17308. Epub 2022 Apr 20.
Early spontaneous abortion (ESA) is one of the most common complications during pregnancy and the inflammation condition in uterine environment such as long-term exposure to high TNFα plays an essential role in the aetiology. Ferritin heavy chain (FTH1) is considered to be closely associated with inflammation and very important in normal pregnancy, yet the underlying mechanism of how TNFα induced abortion and its relationship with FTH1 remain elusive. In this study, we found that TNFα and FTH1 were positively expressed in decidual stromal cells and increased significantly in the ESA group compared with the normal pregnancy group (NP group). Besides, TNFα expression was positively correlated with FTH1 expression. Furthermore, in vitro cell model demonstrated that high TNFα could induce the abnormal signals of TNFR/NF-κB/FTH1 and activate apoptosis both in human endometrium stromal cells (hESCs) and in local decidual tissues. Taken together, the present findings suggest that the excessive apoptosis in response to TNFα-induced upregulation of FTH1 may be responsible for the occurrence of ESA, and thus provide a possible therapeutic target for the treatment of ESA.
早期自发性流产（ESA）是妊娠期间最常见的并发症之一，子宫环境中的炎症状态，如长期暴露于高 TNFα，在发病机制中起着至关重要的作用。铁蛋白重链（FTH1）被认为与炎症密切相关，在正常妊娠中非常重要，但 TNFα 诱导流产的潜在机制及其与 FTH1 的关系仍不清楚。在这项研究中，我们发现 TNFα 和 FTH1 在蜕膜基质细胞中呈阳性表达，并且在 ESA 组中与正常妊娠组（NP 组）相比显著增加。此外，TNFα 表达与 FTH1 表达呈正相关。此外，体外细胞模型表明，高 TNFα 可诱导人子宫内膜基质细胞（hESCs）和局部蜕膜组织中 TNFR/NF-κB/FTH1 的异常信号，并激活细胞凋亡。综上所述，这些发现表明，TNFα 诱导的 FTH1 上调引起的过度凋亡可能是 ESA 发生的原因，并为 ESA 的治疗提供了一个可能的治疗靶点。
