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The impact of junk food on male fertility: therapeutic interventions targeting advanced glycation end-products and oxidative stress in mice
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  • Published: 14 March 2026

The impact of junk food on male fertility: therapeutic interventions targeting advanced glycation end-products and oxidative stress in mice

  • Z. Darmishonnejad1,2,
  • V. Hassan Zadeh2,
  • M. Tavalaee1,
  • A. Moazamian3,4,
  • R. J. Aitken5,
  • J. R. Drevet3,
  • P. Gharagozloo4 &
  • …
  • M. H. Nasr-Esfahani1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Diseases
  • Physiology

Abstract

Frequent consumption of poor-quality diets “junk food” leads to the accumulation of sugar-derived advanced glycation end-products (AGEs), promoting inflammation and oxidative stress (i.e., diminished endogenous antioxidant defenses). This biology has been linked to reduced male fertility, but it is unclear whether reversing AGE damage or boosting antioxidant defenses can restore reproductive function. We used a mouse model to test two approaches: Alagebrium (ALT-711), an investigational drug which breaks AGE cross-links, and Fertilix®, an antioxidant micronutrient blend. Sixty-eight male C57BL/6 mice were fed either a standard or AGE-rich diet, then treated for 35 days and mated. The AGE-rich diet raised glycation and metabolic markers, increased oxidative stress, disrupted spermatogenesis, and produced poorer sperm (lower counts and motility, more DNA damage). These changes translated into fewer pregnancies, more miscarriages, and smaller litters. Both interventions corrected many redox-related sperm defects, but only Fertilix® restored reproductive outcomes to near normal levels in AGE-fed animals; ALT-711 improved some measures yet did not rescue fertility and in fact worsened pregnancy metrics in healthy controls. These findings implicate AGE-driven oxidative stress as a modifiable driver of diet-related male infertility and support targeted antioxidant repletion to restore fertility; confirmation in clinical trials, albeit challenging, is warranted.

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Data availability

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

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Funding

The program was jointly funded by the Royan Institute for Biotechnology, ACECR, Isfahan, Iran and CellOxess, a biotechnology with a commercial interest in the detection and resolution of oxidative stress.

Author information

Authors and Affiliations

  1. Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran, Islamic Republic of

    Z. Darmishonnejad, M. Tavalaee & M. H. Nasr-Esfahani

  2. Department of Cell and Molecular Biology, Faculty of Biology, College of Science, University of Tehran, Tehran, Iran, Islamic Republic of

    Z. Darmishonnejad & V. Hassan Zadeh

  3. EVALSEM- iGReD- CRBC- Faculté de Médecine, Université Clermont Auvergne, Clermont Ferrand, France

    A. Moazamian & J. R. Drevet

  4. Research & Development, CellOxess Biotechnology, Ewing, USA

    A. Moazamian & P. Gharagozloo

  5. Priority Research Centre for Reproductive Science, University of Newcastle, Newcastle, Australia

    R. J. Aitken

Authors
  1. Z. Darmishonnejad
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  2. V. Hassan Zadeh
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  3. M. Tavalaee
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  4. A. Moazamian
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  5. R. J. Aitken
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  6. J. R. Drevet
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  7. P. Gharagozloo
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  8. M. H. Nasr-Esfahani
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Contributions

ZD: Investigation, Methodology, Project Administration, Writing—Original Draft; VHZ: Investigation, Resources; MT: Conceptualization, Investigation, Project Administration, Resources, Writing—Original Draft, Writing—Review & Editing; AM: Visualization, Writing—Review & Editing; RJA: Writing—Review & Editing; JRD: Methodology, Writing—Original Draft, Review & Editing; PG: Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing; MHNE: Conceptualization, Methodology, Project Administration, Supervision, Writing—Original Draft, Writing—Review & Editing.

Corresponding authors

Correspondence to P. Gharagozloo or M. H. Nasr-Esfahani.

Ethics declarations

Competing interests

AM and PG are employees of CellOxess Biotechnology. RJA and JRD are honorary scientific advisors to CellOxess Biotechnology. The remaining authors have no disclosures.

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Cite this article

Darmishonnejad, Z., Hassan Zadeh, V., Tavalaee, M. et al. The impact of junk food on male fertility: therapeutic interventions targeting advanced glycation end-products and oxidative stress in mice. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42820-5

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  • Received: 13 August 2025

  • Accepted: 27 February 2026

  • Published: 14 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-42820-5

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Keywords

  • High-fat diet
  • Advanced glycation end-products
  • Oxidative stress
  • Antioxidant micronutrients
  • Sperm DNA damage
  • Male infertility
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