Work

Dexamethasone Promotes Autophagy Dependent Ferroptosis of Placental Trophoblast Cells Through GRα

Year: 2025

Type: article

Abstract: Dexamethasone (DEX) has been extensively employed for the treatment of pregnancy disorders related to preterm birth. However, the precise mechanism by which prenatal DEX exposure affects foetal development remains unclear. This study delves into investigating the influence of DEX and ferroptosis inhibitors on the activity and ferroptosis level of placental trophoblast cells through various in vitro tests. The results demonstrated that prenatal administration of DEX led to a substantially increased ferroptosis level in placental tissues. DEX decreased cell viability, increased iron accumulation and increased lipid peroxidation. Treatment with ferroptosis inhibitors reversed these effects. Mechanistically, DEX regulated autophagy and modulated the protein levels of AMPKα/BECN1 and ATG5/ATG7/NCOA4 signalling pathways by inhibiting its receptor GRα. Additionally, autophagy activation mediated through the AMPKα/BECN1 axis and ferritin degradation via ATG5/ATG7/NCOA4 signalling was associated with DEX-induced ferroptosis. Overall, this study provides experimental evidence supporting the detrimental side effects of DEX on preterm pregnancy-related disorders. It identified that AMPKα/BECN1 and ATG5/ATG7/NCOA4 were key pathways by which DEX induced autophagy-dependent ferroptosis in placental trophoblast cells.

Source: Journal of Cellular and Molecular Medicine

DOI: 10.1111/jcmm.70613

Authors: Junlei Lu, Xinyun Huang, Yuan Xu, Qiaoping Xu, Hongkai Shang

Institutions: Zhejiang Chinese Medical University, Zhejiang University, Hangzhou Xiaoshan Second People's Hospital, Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,210