ArticleThe Journal of biological chemistry2009
Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 230 citations in OpenAlex.
- Bioinspired zinc-doped carbon dots protect against polystyrene microplastic-induced spermatogenic dysfunction through Nrf2 activation and cuproptosis suppression.Materials today. Bio · 2026Article
- Ferroptosis in health and disease.Molecular biomedicine · 2026Review
- Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Differential expression of ALOX15 and GPX4 in the testicular tissue of men with obstructive and non-obstructive azoospermia: a cross-sectional study.Translational andrology and urology · 2026Article
- Gut Microbial Dysbiosis and Male Reproductive Health: Current Insights and Future Directions.International journal of molecular sciences · 2026Review
- Mechanistic insights into ferroptosis in thyroid cancer and its therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Sperm mitochondrial sheath formation - how and why?Nature reviews. Urology · 2026Review
- Meiotic prophase I disruption as a strategy for nonhormonal male contraception using small-molecule inhibitor JQ1.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Altered transposon element-derived genes distort oxygen-free radical scavenger systems in FXD.NAR molecular medicine · 2026Article
- Ferroptosis and microglial polarization in retinal vein occlusion: pathological mechanisms and therapeutic strategies.International journal of ophthalmology · 2026Review
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Beyond catalysis: Spatial topology of GPX4 in ferroptosis and its theranostic implications.Theranostics · 2026Article
- Dietary supplementation of male mice with inorganic, organic or nanoparticle selenium preparations: evidence supporting a putative gut-thyroid-male fertility axis.Redox report : communications in free radical research · 2025Article
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm.Nature communications · 2025Article
- Recommendations for robust and reproducible research on ferroptosis.Nature reviews. Molecular cell biology · 2025Review
- Androgen-induced ferroptosis regulates seasonal testicular regression: insights into adaptive mechanisms of seasonal breeding.BMC genomics · 2025Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674-683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermatocyte-specific GPx4 knock-out mice using a Cre-loxP system. All the spermatocyte-specific GPx4 knock-out male mice were found to be infertile despite normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. Isolated epididymal GPx4-null spermatozoa could not fertilize oocytes in vitro. These spermatozoa showed significant reductions of forward motility and the mitochondrial membrane potential. These impairments were accompanied by the structural abnormality, such as a hairpin-like flagella bend at the midpiece and swelling of mitochondria in the spermatozoa. These results demonstrate that the depletion of GPx4 in spermatocytes causes severe abnormalities in spermatozoa. This may be one of the causes of male infertility in mice and humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.