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Microwave exposure induced ferroptosis by inhibiting the Nrf2 pathway and affected reproductive function in male mice
Jingchao Gao1, Xinyue Li2, Yizhuo Hou3
1Beijing Institute of Radiation Medicine, Beijing 100850, China; Department of Oncology, Air Force Medical Center of the PLA, Beijing 100142, China.
Abstract:
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.
Insights
Microwave exposure harms male fertility by increasing oxidative stress and inducing ferroptosis, a cell death pathway. This occurs through the inhibition of the Nrf2 signaling pathway, impacting key proteins like SLC7A11 and GPX4.
Area of Science:
- Reproductive Biology
- Toxicology
- Cellular Biology
Background:
- The negative health effects of microwave exposure on male reproduction are not fully understood.
- Investigating the mechanisms of microwave-induced reproductive damage is crucial for public health.
Purpose of the Study:
- To explore the role of ferroptosis in microwave-induced reproductive damage.
- To elucidate the regulatory mechanisms of ferroptosis in response to microwave exposure.
Main Methods:
- Male C57 mice and GC-2 spermatocytes were exposed to microwave radiation (2.856 GHz).
- Assessed sperm motility, morphology, testicular and mitochondrial damage, oxidative stress markers (MDA, GSH/GSSG), iron levels, and protein expressions (SLC7A11, GPX4, Nrf2, Keap1, HO-1).
- Utilized the ferroptosis inhibitor Fer-1 and Western blotting for mechanistic analysis.
Main Results:
- Microwave exposure decreased sperm motility, altered morphology, damaged testicular tissue, and increased oxidative stress markers.
- Increased Fe²⁺ levels and decreased SLC7A11 and GPX4 expressions were observed, indicating ferroptosis induction.
- Fer-1 treatment reversed these effects, improving cell viability and reducing oxidative stress, while up-regulating Nrf2 pathway proteins.
Conclusions:
- Microwave exposure impairs male reproductive function by inducing oxidative stress and ferroptosis.
- The Nrf2 signaling pathway plays a key role in regulating ferroptosis, with its inhibition by microwaves leading to reduced SLC7A11 and GPX4 expression.
- These findings highlight ferroptosis as a critical mediator of microwave-induced male reproductive toxicity.
