{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:05:45Z","timestamp":1785510345225,"version":"3.56.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:p>\n                    Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (\n                    <jats:italic>AK9<\/jats:italic>\n                    ) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and\/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2305712120","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T15:09:14Z","timestamp":1696864154000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["Adenylate kinase 9 is essential for sperm function and male fertility in mammals"],"prefix":"10.1073","volume":"120","author":[{"given":"Elena","family":"O\u2019Callaghan","sequence":"first","affiliation":[{"name":"Animal and Crop Sciences, School of Agriculture and Food Science, University College Dublin, Belfield, Dublin D04 V1W8, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7093-2191","authenticated-orcid":false,"given":"Paula","family":"Navarrete-Lopez","sequence":"additional","affiliation":[{"name":"Departamento de Reproducci\u00f3n 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