ArticleReproductive medicine and biology
KEAP1-NRF2 system regulates age-related spermatogenesis dysfunction.
Article in Reproductive medicine and biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The impact of animal models on translating male infertility research from bench to bedside: a narrative review.Reproductive biology and endocrinology : RB&E · 2026Review
- Ferulic acid relieves hypoxic damage by inhibiting endoplasmic reticulum stress, oxidative stress, and apoptosis through activating FOXA2-modulated Nrf2/HO-1 pathway in spermatogonial cells.Journal of bioenergetics and biomembranes · 2026Article
- Silicon-Based Agent Attenuates Age-Related Spermatogenesis Disorder.International journal of urology : official journal of the Japanese Urological Association · 2025Article
- KEAP1-NRF2 system regulates age-related spermatogenesis dysfunction.Reproductive medicine and biologyArticle
- Redox Imbalance in Male Infertility: From Empirical Antioxidant Therapy to Precision Medicine and Epigenetic Insights.Reproductive medicine and biologyReview
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Authors and funding
12 authors.
Funding
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Abstract
Purpose: The average fatherhood age has been consistently increasing in developed countries. Aging has been identified as a risk factor for male infertility. However, its impact on various mechanisms remains unclear. This study focused on the KEAP1-NRF2 oxidative stress response system, by investigating the relationship between the KEAP1-NRF2 system and age-related changes in spermatogenesis. Methods: For examination of age-related changes, we used 10-, 30-, 60-, and 90-week-old mice to compare sperm count, sperm motility, and protein expression. For assessment of Keap1 inhibition, 85-week-old C57BL/6J mice were randomly assigned to the following groups: control and bardoxolone methyl (KEAP1 inhibitor). Whole-exome sequencing of a Japanese cohort of patients with non-obstructive azoospermia was performed for evaluating. Results: Sperm count decreased significantly with aging. Oxidative stress and KEAP1 expression in the testes were elevated. Inhibition of KEAP1 in aging mice significantly increased sperm count compared with that in the control group. In the human study, the frequency of a missense-type SNP (rs181294188) causing changes in NFE2L2 (NRF2) activity was significantly higher in patients with non-obstructive azoospermia than in healthy control group. Conclusions: The KEAP1-NRF2 system, an oxidative stress response system, is associated with age-related spermatogenesis dysfunction.
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