Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice

The mechanisms underlying the negative health effects of microwave exposure on male reproduction remain unclear. Thus, this study aimed to explore the role and regulatory mechanisms of ferroptosis in microwave-induced reproductive damage. The exposure of male C57 mice to 2.856 GHz of microwave radia...

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Main Authors: Jingchao Gao, Xinyue Li, Yizhuo Hou, Yanyang Li, Yueyue Pang, Xiaoran Wu, Li Zhao, Jing Zhang, Haoyu Wang, Hui Wang, Ji Dong, Xinping Xu, Ruiyun Peng, Yu Wang, Binwei Yao
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325008681
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author Jingchao Gao
Xinyue Li
Yizhuo Hou
Yanyang Li
Yueyue Pang
Xiaoran Wu
Li Zhao
Jing Zhang
Haoyu Wang
Hui Wang
Ji Dong
Xinping Xu
Ruiyun Peng
Yu Wang
Binwei Yao
author_facet Jingchao Gao
Xinyue Li
Yizhuo Hou
Yanyang Li
Yueyue Pang
Xiaoran Wu
Li Zhao
Jing Zhang
Haoyu Wang
Hui Wang
Ji Dong
Xinping Xu
Ruiyun Peng
Yu Wang
Binwei Yao
author_sort Jingchao Gao
collection DOAJ
description The mechanisms underlying the negative health effects of microwave exposure on male reproduction remain unclear. Thus, this study aimed to explore the role and regulatory mechanisms of ferroptosis in microwave-induced reproductive damage. The exposure of male C57 mice to 2.856 GHz of microwave radiation at 0, 10 and 20 mW/cm² for 30 min decreased sperm motility, induced morphological changes, damaged testicular tissue and mitochondrial morphology, increased malondialdehyde (MDA) contents and decreased the GSH/GSSG ratio. Simultaneously, the Fe²⁺ levels increased and SLC7A11 and GPX4 protein expressions decreased, causing oxidative stress. After 30 min of mouse spermatocyte (GC-2) irradiation, the cell viability of the Fer-1 inhibitor group and the GSH/GSSG ratio increased, while the reactive oxygen species, MDA and ferrous iron contents decreased. Furthermore, the depolarisation of membrane potential improved. Western blotting revealed that Nrf2, Keap1, SLC7A11, GPX4 and HO-1 expressions were down-regulated by microwave exposure and significantly up-regulated following the addition of the Fer-1 inhibitor. The results confirmed that the Nrf2 signalling pathway can regulate ferroptosis of oxidative stress. This study demonstrates that microwave exposure affects mouse reproductive function by enhancing oxidative stress, inducing ferroptosis by inhibiting the Nrf2 signalling pathway and reducing SLC7A11 and GPX4 protein expressions.
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spelling doaj-art-5f5e9b49bdc746f4a1b92ce7c80f9baf2025-08-20T02:36:59ZengElsevierEcotoxicology and Environmental Safety0147-65132025-08-0130111852310.1016/j.ecoenv.2025.118523Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male miceJingchao Gao0Xinyue Li1Yizhuo Hou2Yanyang Li3Yueyue Pang4Xiaoran Wu5Li Zhao6Jing Zhang7Haoyu Wang8Hui Wang9Ji Dong10Xinping Xu11Ruiyun Peng12Yu Wang13Binwei Yao14Beijing Institute of Radiation Medicine, Beijing 100850, China; Department of Oncology, Air Force Medical Center of the PLA, Beijing 100142, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, China; School of Public Health, Wannan Medical College, Wuhu 241002, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, China; School of Public Health, Wannan Medical College, Wuhu 241002, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Institute of Radiation Medicine, Beijing 100850, China; Corresponding authors.Department of Oncology, Air Force Medical Center of the PLA, Beijing 100142, China; Corresponding authors.Beijing Institute of Radiation Medicine, Beijing 100850, China; Corresponding authors.The mechanisms underlying the negative health effects of microwave exposure on male reproduction remain unclear. Thus, this study aimed to explore the role and regulatory mechanisms of ferroptosis in microwave-induced reproductive damage. The exposure of male C57 mice to 2.856 GHz of microwave radiation at 0, 10 and 20 mW/cm² for 30 min decreased sperm motility, induced morphological changes, damaged testicular tissue and mitochondrial morphology, increased malondialdehyde (MDA) contents and decreased the GSH/GSSG ratio. Simultaneously, the Fe²⁺ levels increased and SLC7A11 and GPX4 protein expressions decreased, causing oxidative stress. After 30 min of mouse spermatocyte (GC-2) irradiation, the cell viability of the Fer-1 inhibitor group and the GSH/GSSG ratio increased, while the reactive oxygen species, MDA and ferrous iron contents decreased. Furthermore, the depolarisation of membrane potential improved. Western blotting revealed that Nrf2, Keap1, SLC7A11, GPX4 and HO-1 expressions were down-regulated by microwave exposure and significantly up-regulated following the addition of the Fer-1 inhibitor. The results confirmed that the Nrf2 signalling pathway can regulate ferroptosis of oxidative stress. This study demonstrates that microwave exposure affects mouse reproductive function by enhancing oxidative stress, inducing ferroptosis by inhibiting the Nrf2 signalling pathway and reducing SLC7A11 and GPX4 protein expressions.http://www.sciencedirect.com/science/article/pii/S0147651325008681Microwave exposureReproductive damageLipid peroxidationFerroptosisSLC7A11GPX4
spellingShingle Jingchao Gao
Xinyue Li
Yizhuo Hou
Yanyang Li
Yueyue Pang
Xiaoran Wu
Li Zhao
Jing Zhang
Haoyu Wang
Hui Wang
Ji Dong
Xinping Xu
Ruiyun Peng
Yu Wang
Binwei Yao
Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
Ecotoxicology and Environmental Safety
Microwave exposure
Reproductive damage
Lipid peroxidation
Ferroptosis
SLC7A11
GPX4
title Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
title_full Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
title_fullStr Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
title_full_unstemmed Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
title_short Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
title_sort microwave exposure induced ferroptosis by inhibiting the nrf2 pathway and affected reproductive function in male mice
topic Microwave exposure
Reproductive damage
Lipid peroxidation
Ferroptosis
SLC7A11
GPX4
url http://www.sciencedirect.com/science/article/pii/S0147651325008681
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