ArticleEBioMedicine2023
Deficiency in AK9 causes asthenozoospermia and male infertility by destabilising sperm nucleotide homeostasis.
Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Advances in Research on Models of Oligoasthenozoospermia.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Genetic landscape of male infertility: chromosomal abnormalities and Y chromosome microdeletions in a Turkish cohort (1 314 Cases).Human genetics · 2026Article
- Gut dysbiosis induces the development of asthenozoospermia through butanoate metabolism.Frontiers in immunology · 2026Article
- CAPZA1 deficiency disrupts sperm flagellar structure and motility, potentially involving the p300/SLC7A11 pathway.Frontiers in endocrinology · 2026Article
- Cross-omics association of small extracellular vesicle miRNAs and metabolites in seminal plasma of idiopathic male infertility.Frontiers in endocrinology · 2026Article
- Mutations in CFAP57 disrupt the localization of MYH10 and IFT88, leading to flagellogenesis failure in humans and mice.Human genomics · 2025Article
- Reproductive physiological impacts of high ambient temperature on animals: the impaired testicular function and compromised sperm quality in C57BL/6 mice.Biological research · 2025Article
- Predicting protein-protein interactions in the human proteome.Science (New York, N.Y.) · 2025Article
- Of mice and men: translating mouse knockout models of human male infertility.Reproduction (Cambridge, England) · 2025Review
- Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans.Human genetics · 2025Article
- Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility.Nature communications · 2025Article
- Heterogeneity of radial spoke components in Tetrahymena cilia.Cellular and molecular life sciences : CMLS · 2025Article
- Mouse radial spoke 3 is a metabolic and regulatory hub in cilia.Nature structural & molecular biology · 2025Article
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- Baicalin targets YTHDC2 and alleviates male reproductive toxicity caused by co-exposure to nanoplastics and manganese through mJournal of nanobiotechnology · 2025Article
- Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium.Toxics · 2025Article
- Associations between seminal plasma osteopontin level and sperm motility in infertile men with asthenozoospermia.Frontiers in endocrinology · 2025Article
- Acupuncture mediates the "gut-testis axis" to improve asthenozoospermia.Frontiers in endocrinology · 2025Article
- Novel Genes of the Male Reproductive System: Potential Roles in Male Reproduction and as Non-hormonal Male Contraceptive Targets.Molecular reproduction and development · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAsthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the testes of humans and mice and encodes a type of adenosine kinase that is functionally involved in cellular nucleotide homeostasis and energy metabolism. We aimed to assess whether AK9 is involved in asthenozoospermia.
methodsOne-hundred-and-sixty-five Chinese men with idiopathic asthenozoospermia were recruited. Whole-exome sequencing (WES) and Sanger sequencing were performed for genetic analyses. Papanicolaou staining, Haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were used to observe the sperm morphology and structure. Ak9-knockout mice were generated using CRISPR-Cas9. Sperm adenosine was detected by liquid chromatography-mass spectrometry. Targeted sperm metabolomics was performed. Intracytoplasmic sperm injection (ICSI) was used to treat patients.
findingsWe identified five patients harbouring bi-allelic AK9 mutations. Spermatozoa from men harbouring bi-allelic AK9 mutations have a decreased ability to sustain nucleotide homeostasis. Moreover, bi-allelic AK9 mutations inhibit glycolysis in sperm. Ak9-knockout male mice also presented similar phenotypes of asthenozoospermia. Interestingly, ICSI was effective in bi-allelic AK9 mutant patients in achieving good pregnancy outcomes.
interpretationDefects in AK9 induce asthenozoospermia with defects in nucleotide homeostasis and energy metabolism. This sterile phenotype could be rescued by ICSI.
fundingThe National Natural Science Foundation of China (82071697), Medical Innovation Project of Fujian Province (2020-CXB-051), open project of the NHC Key Laboratory of Male Reproduction and Genetics in Guangzhou (KF202004), Medical Research Foundation of Guangdong Province (A2021269), Guangdong Provincial Reproductive Science Institute Innovation Team grants (C-03), and Outstanding Young Talents Program of Capital Medical University (B2205).
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