ArticleProceedings of the National Academy of Sciences of the United States of America2011
Na,K-ATPase alpha4 isoform is essential for sperm fertility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Sperm Ion Transporters and Channels in Human Asthenozoospermia: Genetic Etiology, Lessons from Animal Models, and Clinical Perspectives.International journal of molecular sciences · 2022Pooled it
- Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.Clinical genetics · 2026Article
- The systems that transport ions and their impact on sperm function and male fertility.Function (Oxford, England) · 2026Review
- Expression and regulation of lncRNAs in the testes of Yili geese with high and low sperm motility.BMC genomics · 2026Article
- The Sperm Acrosomal Reaction Depends on the Function of Both Na,K-ATPase α1 and α4 Isoforms.International journal of molecular sciences · 2026Article
- Pathophysiological Roles of Two Intracellular P-Type ATPases: The Cancer-Associated NaInternational journal of molecular sciences · 2026Review
- Parallel Erosion of a Testis-Specific Na+/K+ ATPase in Three Mammalian Lineages Sheds Light into the Evolution of Spermatozoa Energetics.Genome biology and evolution · 2026Article
- Na+,K+-ATPase α isoforms in sperm show a highly structured and distinct pattern of distribution.Reproduction (Cambridge, England) · 2025Article
- Membrane proteome analysis identifies key components of sensing in Phytophthora parasitica zoospores.Scientific reports · 2025Article
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- Strategies to Develop Na,K-ATPase-α4 Inhibitors as Male Contraceptives.International journal of molecular sciences · 2025Article
- Alpha4 Na,K-ATPase Localization and Expression Are Dynamic Aspects of Spermatogenesis and in Sperm Incubated Under Capacitating Conditions.International journal of molecular sciences · 2025Article
- Non-hormonal Contraception: Current and Emerging Targets.Advances in experimental medicine and biology · 2025Review
- Molecular Structure of the NaInternational journal of molecular sciences · 2024Article
- Mapping the proteome landscape of Indian Zebu (Sahiwal) spermatozoa using high-resolution mass spectrometry andAnimal biotechnology · 2024Article
- The lethal homozygous variant in the ATP1A2 gene is associated with FARIMPD syndrome phenotypes in newborns.Neurogenetics · 2024Article
- Advances in Male Contraception: When Will the Novel Male Contraception be Available?The world journal of men's health · 2024Review
- Differential protein repertoires related to sperm function identified in extracellular vesicles (EVs) in seminal plasma of distinct fertility buffalo (Frontiers in cell and developmental biology · 2024Article
- The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.Clinical science (London, England : 1979) · 2023Review
- Proteomic Analysis of Frozen-Thawed Spermatozoa with Different Levels of Freezability in Dairy Goats.International journal of molecular sciences · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of ion balance in spermatozoa has been shown to be essential for sperm motility and fertility. Control of intracellular ion levels requires the function of distinct ion-transport mechanisms at the cell plasma membrane. Active Na(+) and K(+) exchange in sperm is under the control of the Na,K-ATPase. Two molecular variants of the catalytic subunit of the Na,K-ATPase, α1 and α4, coexist in sperm. These isoforms exhibit different biochemical properties; however, their function in sperm fertility is unknown. In this work, we show that Na,K-ATPase α4 is essential for sperm fertility. Knockout male mice lacking α4 are completely sterile and spermatozoa from these mice are unable of fertilizing eggs in vitro. Furthermore, α4 deletion results in severe reduction in sperm motility and hyperactivation typical of sperm capacitation. In addition, absence of α4 causes a characteristic bend in the sperm flagellum, indicative of abnormal sperm ion regulation. Accordingly, α4-null sperm present increased intracellular Na(+) and cell plasma membrane depolarization. These results are unique in demonstrating the absolute requirement of α4 for sperm fertility. Moreover, the inability of α1 to compensate for α4 suggests that α4 is the Na,K-ATPase-α isoform directly involved in sperm fertility. Our findings show α4 as an attractive target for male contraception and open the possibility for the potential use of this Na,K-ATPase isoform as a biomarker for male fertility.
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Registered trials
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.