{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:17:38Z","timestamp":1790651858578,"version":"4.1.0"},"reference-count":17,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thanks to the analysis of an Interspecific Recombinant Congenic Strain (IRCS), we previously defined the Mafq1 quantitative trait locus as an interval on mouse Chromosome 1 associated with male hypofertility and ultrastructural abnormalities. We identified the Spermatogenesis associated protein 3 gene (Spata3 or Tsarg1) as a pertinent candidate within the Mafq1 locus and performed the CRISPR-Cas9 mediated complete deletion of the gene to investigate its function. Male mice deleted for Spata3 were normally fertile in vivo but exhibited a drastic reduction of efficiency in in vitro fertilization assays. Mobility parameters were normal but ultrastructural analyses revealed acrosome defects and an overabundance of lipids droplets in cytoplasmic remnants. The deletion of the Spata3 gene reproduces therefore partially the phenotype of the hypofertile IRCS strain.<\/jats:p>","DOI":"10.3390\/ijms22041959","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T08:09:09Z","timestamp":1613462949000},"page":"1959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Deletion of the Spata3 Gene Induces Sperm Alterations and In Vitro Hypofertility in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Marie-Sophie","family":"Girault","sequence":"first","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00f4me","family":"Ialy-Radio","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Stouvenel","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Viollet","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Pierre","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryline","family":"Favier","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-3831","authenticated-orcid":false,"given":"Ahmed","family":"Ziyyat","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"},{"name":"Service d\u2019Histologie, d\u2019Embryologie, Biologie de la Reproduction, AP-HP, H\u00f4pital Cochin, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Barbaux","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 de Paris, INSERM, CNRS, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12201","DOI":"10.1073\/pnas.1635054100","article-title":"A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets","volume":"100","author":"Schultz","year":"2003","journal-title":"Proc. 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PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003363"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1086\/521314","article-title":"Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia","volume":"81","author":"Dam","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/aja.2010.47","article-title":"A newly discovered mutation in PICK1 in a human with globozoospermia","volume":"12","author":"Liu","year":"2010","journal-title":"Asian J. Androl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/molehr\/gar057","article-title":"Association of mutations in the zona pellucida binding protein 1 (ZPBP1) gene with abnormal sperm head morphology in infertile men","volume":"18","author":"Yatsenko","year":"2012","journal-title":"Mol. Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vatin, M., Girault, M.S., Firlej, V., Marchiol, C., Ialy-Radio, C., Montagutelli, X., Vaiman, D., Barbaux, S., and Ziyyat, A. (2020). Identification of a New QTL Region on Mouse Chromosome 1 Responsible for Male Hypofertility: Phenotype Characterization and Candidate Genes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228506"},{"key":"ref_8","first-page":"25","article-title":"Molecular cloning for testis spermatogenesis cell apoptosis related gene TSARG1 and Mtsarg1 and expression analysis for Mtsarg1 gene","volume":"30","author":"Fu","year":"2003","journal-title":"Yi Chuan Xue Bao"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s11033-008-9276-6","article-title":"Molecular cloning and characterization of a novel transcript variant of Mtsarg1 gene","volume":"36","author":"Li","year":"2009","journal-title":"Mol. Biol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.fertnstert.2013.07.1999","article-title":"Potential biomarkers of nonobstructive azoospermia identified in microarray gene expression analysis","volume":"100","author":"Malcher","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17173","DOI":"10.1038\/s41598-019-53445-2","article-title":"An exome-wide rare variant analysis of Korean men identifies three novel genes predisposing to prostate cancer","volume":"9","author":"Oh","year":"2019","journal-title":"Sci. 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Biol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Barraud-Lange, V., Ialy-Radio, C., Chalas, C., Holtzmann, I., Wolf, J.P., Barbaux, S., and Ziyyat, A. (2020). Partial Sperm beta1 Integrin Subunit Deletion Proves its Involvement in Mouse Gamete Adhesion\/Fusion. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228494"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.1038\/s41598-020-62091-y","article-title":"Sperm SPACA6 protein is required for mammalian Sperm-Egg Adhesion\/Fusion","volume":"10","author":"Barbaux","year":"2020","journal-title":"Sci. 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