TNFα-induced abnormal activation of TNFR/NF-κB/FTH1 in endometrium is involved in the pathogenesis of early spontaneous abortion.

Abstract

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.

• Authors: Yuting Wen, Meng Cheng, Lang Qin, Wenming Xu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 26 Issue 10 Pg. 2947-2958 (05 2022) ISSN: 1582-4934 [Electronic] England
• PMID: 35441429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 West China Second University Hospital, Sichuan University. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• NF-kappa B
• Tumor Necrosis Factor-alpha
• Ferritins
• FTH1 protein, human
• Oxidoreductases

Topics

• Abortion, Spontaneous
• Endometrium (metabolism)
• Female
• Ferritins (metabolism)
• Humans
• Inflammation
• NF-kappa B (metabolism)
• Oxidoreductases (metabolism)
• Pregnancy
• Tumor Necrosis Factor-alpha (pharmacology)