Melatonin ameliorates RF-EMR-induced reproductive damage by inhibiting ferroptosis through Nrf2 pathway activation

PAPER manual Pathology Research and Practice 2025 Animal study Effect: mixed Evidence: Low

Read original paper → DOI: 10.1016/j.prp.2025.156003 PMID: 40344840 Evidence Lab

Abstract

Category: Reproductive Toxicology Tags: RF-EMR, melatonin, ferroptosis, Nrf2 pathway, oxidative stress, male reproduction, fertility DOI: 10.1016/j.prp.2025.156003 URL: pubmed.ncbi.nlm.nih.gov Overview In recent years, growing evidence has highlighted significant concerns regarding the hazardous effects of radiofrequency electromagnetic radiation (RF-EMR) on male reproductive function. The search for viable protective agents to counteract these effects has brought attention to melatonin, known for its antioxidant and anti-apoptotic properties and its role in reproductive health. Yet, the molecular pathways through which melatonin shields against RF-EMR-induced reproductive damage have remained elusive. Findings - Prolonged exposure (8 weeks) to RF-EMR (2.45 GHz; power density 2.5 W/m2; SAR 0.125-0.5 W/kg) led to increased oxidative stress and ferroptosis in testicular tissue of male mice. - The resulting oxidative damage from RF-EMR caused notable decreases in sperm quality. - Administering melatonin notably reduced the testicular oxidative injury and inhibited ferroptosis induced by RF-EMR. - Mechanistic studies demonstrated that melatonin counters reactive oxygen species (ROS) production and ferroptosis by activating the Nrf2 signaling pathway through MT1/MT2 receptors. Conclusion RF-EMR exposure is directly linked to harmful effects on male reproduction, primarily via ferroptosis in testicular tissue. Melatonin substantially protects against this RF-EMR-induced damage by activating the Nrf2 pathway, thereby suppressing ferroptosis. These results underscore the potential of melatonin as a therapeutic agent for male infertility linked to RF-EMR exposure. Further controlled trials are recommended to assess melatonin’s clinical benefit in addressing male reproductive damage caused by electromagnetic fields.

AI evidence extraction

At a glance

Study type

Animal study

Effect direction

mixed

Population

Male mice

Sample size

—

Exposure

RF · 2450 MHz · 8 weeks

Evidence strength

Low

Confidence: 98% · Peer-reviewed: yes

Main findings

Eight weeks of whole-body RF-EMR exposure at 2.45 GHz, 2.5 W/m², and SAR 0.125–0.5 W/kg induced ferroptosis and oxidative stress in testicular tissue and reduced sperm quality in male mice. Melatonin mitigated these effects by inhibiting ROS production and ferroptosis through MT1/MT2-mediated activation of the Nrf2 signaling pathway.

Outcomes measured

Testicular ferroptosis
Testicular oxidative stress
Sperm quality
Reactive oxygen species production
Nrf2 signaling pathway activation
Protective effects of melatonin on testicular damage

Limitations

Animal study; applicability to humans is not established
Sample size was not reported in the abstract
The abstract does not provide quantitative effect estimates

View raw extracted JSON

{
    "study_type": "animal",
    "exposure": {
        "band": "RF",
        "source": null,
        "frequency_mhz": 2450,
        "sar_wkg": null,
        "duration": "8 weeks"
    },
    "population": "Male mice",
    "sample_size": null,
    "outcomes": [
        "Testicular ferroptosis",
        "Testicular oxidative stress",
        "Sperm quality",
        "Reactive oxygen species production",
        "Nrf2 signaling pathway activation",
        "Protective effects of melatonin on testicular damage"
    ],
    "main_findings": "Eight weeks of whole-body RF-EMR exposure at 2.45 GHz, 2.5 W/m², and SAR 0.125–0.5 W/kg induced ferroptosis and oxidative stress in testicular tissue and reduced sperm quality in male mice. Melatonin mitigated these effects by inhibiting ROS production and ferroptosis through MT1/MT2-mediated activation of the Nrf2 signaling pathway.",
    "effect_direction": "mixed",
    "limitations": [
        "Animal study; applicability to humans is not established",
        "Sample size was not reported in the abstract",
        "The abstract does not provide quantitative effect estimates"
    ],
    "evidence_strength": "low",
    "confidence": 0.979999999999999982236431605997495353221893310546875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency electromagnetic radiation",
        "RF-EMR",
        "2.45 GHz",
        "melatonin",
        "male reproduction",
        "sperm quality",
        "testicular damage",
        "ferroptosis",
        "oxidative stress",
        "reactive oxygen species",
        "Nrf2",
        "MT1",
        "MT2",
        "mice"
    ],
    "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract/metadata and may be incomplete or incorrect. This content is for informational purposes only and is not medical advice.

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