ArticleBiology of reproduction2011
Mice lacking the USP2 deubiquitinating enzyme have severe male subfertility associated with defects in fertilization and sperm motility.
Article in Biology of reproduction, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- USP2 Attenuates Spermatogenic Cell Apoptosis Via PINK1/Parkin-Dependent Mitophagy in Varicocoele: A Functional Study.Andrology · 2026Article
- Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models.Biomedicines · 2026Review
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- Testicular macrophages: core immune regulators and emerging therapeutic targets in spermatogenic dysfunction.Frontiers in immunology · 2026Review
- Suppression of USP2 in mouse skeletal muscle: a model of oxidative stress in muscle tissue.Experimental animals · 2026Article
- The Deubiquitinase USP2 Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus.Journal of neurochemistry · 2025Article
- Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping Review.Open access journal of contraception · 2025Review
- Essential role of germ cell glycerol-3-phosphate phosphatase for sperm health, oxidative stress control and male fertility in mice.Molecular metabolism · 2024Article
- USP2 Mitigates Reactive Oxygen Species-Induced Mitochondrial Damage via UCP2 Expression in Myoblasts.International journal of molecular sciences · 2024Article
- Biomarker-based human and animal sperm phenotyping: the good, the bad and the ugly†.Biology of reproduction · 2024Review
- USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.Cell death and differentiation · 2023Article
- Targeting the deubiquitinaseOncology reports · 2023Review
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
- Review
- Review
- Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies.Frontiers in endocrinology · 2022Review
- The Conceivable Functions of Protein Ubiquitination and Deubiquitination in Reproduction.Frontiers in physiology · 2022Review
- The cryopreservation process induces alterations in proteins associated with bull sperm quality: The equilibration process could be a probable critical control point.Frontiers in endocrinology · 2022Article
- Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm.Cellular and molecular life sciences : CMLS · 2021Article
- USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes.International journal of molecular sciences · 2021Review
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12 authors.
Funding
Abstract
The ubiquitin-proteasome system plays an important role in spermatogenesis. However, the functions of deubiquitinating enzymes in this process remain poorly characterized. We previously showed that the deubiquitinating enzyme USP2 is induced in late elongating spermatids. To identify its function, we generated mice lacking USP2. Usp2 -/- mice appeared normal, and the weights of major organs, including the testis, did not differ from wild type (Usp2 +/+). However, although the numbers of testicular spermatids and epididymal spermatozoa were normal in Usp2 -/- males, these animals had a severe defect in fertility, yielding only 12% as many offspring as Usp2 +/+ littermates. Spermatogenesis in Usp2 -/- mice was morphologically normal except for the presence of abnormal aggregations of elongating spermatids and formation of multinucleated cells in some tubules. The epididymal epithelium was morphologically normal in Usp2 -/- mice, but some abnormal cells other than sperm were present in the lumen. Usp2 -/- epididymal spermatozoa manifested normal motility when incubated in culture media, but rapidly became immotile when incubated in PBS in contrast to Usp2 +/+ spermatozoa, which largely maintained motility under this condition. Usp2 -/- and +/+ spermatozoa underwent acrosome reactions in vitro with similar frequency. In vitro fertilization assays demonstrated a severe defect in the ability of Usp2 -/- spermatozoa to fertilize eggs. This could be bypassed by intracytoplasmic sperm injection or removal of the zona pellucida, which resulted in fertilization rates similar to that of Usp2 +/+ mice. We demonstrate for the first time, using mouse transgenic approaches, a role for the ubiquitin system in fertilization.
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