{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:23:41Z","timestamp":1783689821209,"version":"3.55.0"},"reference-count":133,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972570"],"award-info":[{"award-number":["31972570"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>As the basis of animal reproductive activity, normal spermatogenesis directly determines the efficiency of livestock production. An in-depth understanding of spermatogenesis will greatly facilitate animal breeding efforts and male infertility treatment. With the continuous development and application of gene editing technologies, they have become valuable tools to study the mechanism of spermatogenesis. Gene editing technologies have provided us with a better understanding of the functions and potential mechanisms of action of factors that regulate spermatogenesis. This review summarizes the applications of gene editing technologies, especially CRISPR\/Cas9, in deepening our understanding of the function of spermatogenesis-related genes and disease treatment. The problems of gene editing technologies in the field of spermatogenesis research are also discussed.<\/jats:p>","DOI":"10.3390\/genes13061000","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T12:48:31Z","timestamp":1654087711000},"page":"1000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Application of CRISPR\/Cas Technology in Spermatogenesis Research and Male Infertility Treatment"],"prefix":"10.3390","volume":"13","author":[{"given":"Hao-Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3996-2509","authenticated-orcid":false,"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"ref_1","unstructured":"Statens Veterin\u00e4rmedicinska Anstalt (2013). Food and agriculture organization of the United Nations."},{"key":"ref_2","unstructured":"Steinfeld, H., Gerber, P., Wassenaar, T.D., Castel, V., Rosales, M., Rosales, M., and de Haan, C. (2006). Livestock\u2019s Long Shadow: Environmental issues and Options, Food & Agriculture Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13567-020-00891-w","article-title":"Progress and challenges in developing organoids in farm animal species for the study of reproduction and their applications to reproductive biotechnologies","volume":"52","author":"Bourdon","year":"2021","journal-title":"Vet. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Saha, S., Roy, P., Corbitt, C., and Kakar, S.S. (2021). Application of Stem Cell Therapy for Infertility. Cells, 10.","DOI":"10.3390\/cells10071613"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-animal-020518-115239","article-title":"Spermatogonial Stem Cell Transplantation: Insights and Outlook for Domestic Animals","volume":"7","author":"Giassetti","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"610888","DOI":"10.3389\/fvets.2021.610888","article-title":"Sperm Functional Genome Associated With Bull Fertility","volume":"8","author":"Ozbek","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1439-0531.2005.00596.x","article-title":"Use of transgenic animals to improve human health and animal production","volume":"40","author":"Houdebine","year":"2005","journal-title":"Reprod. Domest. Anim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.molmed.2005.04.001","article-title":"Developments in transgenic technology: Applications for medicine","volume":"11","author":"Hunter","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0163-7258(03)00069-X","article-title":"Transgenic rabbits as therapeutic protein bioreactors and human disease models","volume":"99","author":"Fan","year":"2003","journal-title":"Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1359-6446(04)03317-3","article-title":"Transgenic chickens as bioreactors for protein-based drugs","volume":"10","author":"Lillico","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e57132","DOI":"10.7554\/eLife.57132","article-title":"CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance","volume":"9","author":"Xu","year":"2020","journal-title":"eLife"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/13.suppl_1.1","article-title":"Spermatogenesis","volume":"13","author":"Loveland","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1242\/dev.146571","article-title":"The nature and dynamics of spermatogonial stem cells","volume":"144","year":"2017","journal-title":"Development"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1530\/REP-13-0466","article-title":"Spermatogonial stem cells from domestic animals: Progress and prospects","volume":"147","author":"Zheng","year":"2014","journal-title":"Reproduction"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: The Commitment to Meiosis","volume":"96","author":"Griswold","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/biolre\/ioy027","article-title":"50 years of spermatogenesis: Sertoli cells and their interactions with germ cells","volume":"99","author":"Griswold","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1006\/scdb.1998.0203","article-title":"The central role of Sertoli cells in spermatogenesis","volume":"9","author":"Griswold","year":"1998","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1095\/biolreprod48.5.952","article-title":"Testicular weight, Sertoli cell number, daily sperm production, and sperm output of sexually mature rabbits after neonatal or prepubertal hemicastration","volume":"48","author":"Thompson","year":"1993","journal-title":"Biol. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/aja.1001880104","article-title":"A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell","volume":"188","author":"Russell","year":"1990","journal-title":"Am. J. Anat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2016.04.009","article-title":"Spermatogenesis in humans and its affecting factors","volume":"59","author":"Neto","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1749-6632.1989.tb25899.x","article-title":"Sertoli-Leydig cell communications","volume":"564","author":"Saez","year":"1989","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1007\/s00018-019-03101-9","article-title":"The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis","volume":"76","author":"Zhou","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.1128\/jb.169.12.5429-5433.1987","article-title":"Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product","volume":"169","author":"Ishino","year":"1987","journal-title":"J. Bacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.molcel.2021.12.002","article-title":"The CRISPR-Cas toolbox and gene editing technologies","volume":"82","author":"Liu","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41580-019-0131-5","article-title":"The next generation of CRISPR-Cas technologies and applications","volume":"20","author":"Gersbach","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrmicro3569","article-title":"An updated evolutionary classification of CRISPR-Cas systems","volume":"13","author":"Makarova","year":"2015","journal-title":"Nat. Rev. Microbiol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.molcel.2015.10.008","article-title":"Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems","volume":"60","author":"Shmakov","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA targeting with CRISPR-Cas13","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/s41580-020-00288-9","article-title":"Applications of CRISPR-Cas in agriculture and plant biotechnology","volume":"21","author":"Zhu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"JCM-01307","DOI":"10.1128\/JCM.01307-18","article-title":"CRISPR-Cas Biology and Its Application to Infectious Diseases","volume":"57","author":"Strich","year":"2019","journal-title":"J. Clin. Microbiol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ydbio.2019.06.017","article-title":"Proteomics and single-cell RNA analysis of Akap4-knockout mice model confirm indispensable role of Akap4 in spermatogenesis","volume":"454","author":"Fang","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1534\/genetics.117.300274","article-title":"Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish","volume":"207","author":"Lin","year":"2017","journal-title":"Genetics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ajhg.2018.12.013","article-title":"Bi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice","volume":"104","author":"Coutton","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.21037\/tau-21-789","article-title":"E3 ubiquitin ligase ASB17 is required for spermiation in mice","volume":"10","author":"Shen","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/jmedgenet-2019-106598","article-title":"Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis","volume":"58","author":"Lu","year":"2021","journal-title":"J. Med. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhou, W., Zhang, P., Gao, F., Zhao, X., Shum, W.W., and Zeng, X. (2021). Cabs1 Maintains Structural Integrity of Mouse Sperm Flagella during Epididymal Transit of Sperm. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020652"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24732","DOI":"10.3390\/ijms161024732","article-title":"CRISPR\/Cas9-Mediated Rapid Generation of Multiple Mouse Lines Identified Ccdc63 as Essential for Spermiogenesis","volume":"16","author":"Young","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e11545","DOI":"10.7717\/peerj.11545","article-title":"T-complex protein 1 subunit zeta-2 (CCT6B) deficiency induces murine teratospermia","volume":"9","author":"Yang","year":"2021","journal-title":"PeerJ"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112178","DOI":"10.1016\/j.yexcr.2020.112178","article-title":"Cdc14a has a role in spermatogenesis, sperm maturation and male fertility","volume":"395","author":"Wen","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/biolre\/ioaa059","article-title":"CIB4 is essential for the haploid phase of spermatogenesis in micedagger","volume":"103","author":"Xu","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1074\/mcp.RA119.001416","article-title":"Integrated Analyses of Phenotype and Quantitative Proteome of CMTM4 Deficient Mice Reveal Its Association with Male Fertility","volume":"18","author":"Liu","year":"2019","journal-title":"Mol. Cell Proteomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8836","DOI":"10.1093\/nar\/gkab619","article-title":"Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility","volume":"49","author":"Charlesworth","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1530\/JOE-19-0438","article-title":"Loss of Cyp11c1 causes delayed spermatogenesis due to the absence of 11-ketotestosterone","volume":"244","author":"Zheng","year":"2020","journal-title":"J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e23367","DOI":"10.1002\/dvg.23367","article-title":"Generation of B6-Ddx4(em1(CreERT2)Utr), a novel CreERT2 knock-in line, for germ cell lineage by CRISPR\/Cas9","volume":"58","author":"Le","year":"2020","journal-title":"Genesis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1096\/fj.201700936R","article-title":"CRISPR\/Cas9-mediated genome editing reveals the synergistic effects of \u03b2-defensin family members on sperm maturation in rat epididymis","volume":"32","author":"Zhang","year":"2018","journal-title":"FASEB J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1095\/biolreprod.114.121418","article-title":"Isolation of doublesex- and mab-3-related transcription factor 6 and its involvement in spermatogenesis in tilapia","volume":"91","author":"Zhang","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12041-021-01264-8","article-title":"DNAH17 is essential for rat spermatogenesis and fertility","volume":"100","author":"Chen","year":"2021","journal-title":"J. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e20182365","DOI":"10.1084\/jem.20182365","article-title":"A DNAH17 missense variant causes flagella destabilization and asthenozoospermia","volume":"217","author":"Zhang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1242\/dev.077982","article-title":"Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus","volume":"139","author":"Pierre","year":"2012","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1093\/biolre\/ioz222","article-title":"Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culturedagger","volume":"102","author":"Yamada","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1093\/biolre\/ioaa082","article-title":"Knockout of family with sequence similarity 170 member A (Fam170a) causes male subfertility, while Fam170b is dispensable in micedagger","volume":"103","author":"Devlin","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3389\/fgene.2018.00732","article-title":"FTO Knockout Causes Chromosome Instability and G2\/M Arrest in Mouse GC-1 Cells","volume":"9","author":"Huang","year":"2018","journal-title":"Front. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1210\/en.2018-00878","article-title":"Loss of Growth Hormone Gene (gh1) in Zebrafish Arrests Folliculogenesis in Females and Delays Spermatogenesis in Males","volume":"160","author":"Hu","year":"2019","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1007\/s43032-020-00395-0","article-title":"Effects of HIF-1alpha on Spermatogenesis of Varicocele Rats by Regulating VEGF\/PI3K\/Akt Signaling Pathway","volume":"28","author":"Wang","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00441-019-03064-0","article-title":"Effect of silencing HIF-1alpha gene on testicle spermatogenesis function in varicocele rats","volume":"378","author":"Zhao","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1016\/j.celrep.2018.11.090","article-title":"Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish","volume":"25","author":"Saju","year":"2018","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1538\/expanim.18-0071","article-title":"Chimeric analysis with newly established EGFP\/DsRed2-tagged ES cells identify HYDIN as essential for spermiogenesis in mice","volume":"68","author":"Oura","year":"2019","journal-title":"Exp. Anim."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1007\/s00018-019-03439-0","article-title":"Regulation of spermatogenesis and reproductive capacity by Igf3 in tilapia","volume":"77","author":"Li","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2021.02.052","article-title":"Deficiency for Lcn8 causes epididymal sperm maturation defects in mice","volume":"548","author":"Wen","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6015","DOI":"10.1007\/s11033-021-06604-6","article-title":"Epididymal initial segment-specific Cre recombinase activity in Lcn8-Cre knock-in mice","volume":"48","author":"Gong","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11148","DOI":"10.1038\/s41598-020-67594-2","article-title":"CRISRP\/Cas9-mediated knockout of Mct8 reveals a functional involvement of Mct8 in testis and sperm development in a rat","volume":"10","author":"Bae","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101312","DOI":"10.1016\/j.jbc.2021.101312","article-title":"A single amino acid mutation in the mouse MEIG1 protein disrupts a cargo transport system necessary for sperm formation","volume":"297","author":"Li","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1172\/JCI36230","article-title":"PICK1 deficiency causes male infertility in mice by disrupting acrosome formation","volume":"119","author":"Xiao","year":"2009","journal-title":"J. Clin. Invest."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yang, D., Xu, J., Chen, K., Liu, Y., Yang, X., Tang, L., Luo, X., Liu, Z., Li, M., and Walters, J.R. (2022). BmPMFBP1 regulates the development of eupyrene sperm in the silkworm, Bombyx mori. PLoS Genet., 18.","DOI":"10.1371\/journal.pgen.1010131"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/biolre\/ioaa041","article-title":"Prss55 but not Prss51 is required for male fertility in micedagger","volume":"103","author":"Kobayashi","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"105517","DOI":"10.1016\/j.jsbmb.2019.105517","article-title":"Rln3a is a prerequisite for spermatogenesis and fertility in male fish","volume":"197","author":"Yang","year":"2020","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_68","first-page":"e21460","article-title":"RNF216 regulates meiosis and PKA stability in the testes","volume":"35","author":"Li","year":"2021","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1093\/biolre\/ioz006","article-title":"RNF216 is essential for spermatogenesis and male fertilitydagger","volume":"100","author":"Melnick","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wei, L., Tang, Y., Zeng, X., Li, Y., Zhang, S., Deng, L., Wang, L., and Wang, D. (2021). The transcription factor Sox30 is involved in Nile tilapia spermatogenesis. J. Genet. Genomics.","DOI":"10.1016\/j.jgg.2021.11.003"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17619","DOI":"10.1038\/s41598-017-17854-5","article-title":"SOX30 is required for male fertility in mice","volume":"7","author":"Feng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fujihara, Y., Oji, A., Larasati, T., Kojima-Kita, K., and Ikawa, M. (2017). Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR\/Cas9-Mediated Mouse Models. Int. J. Mol. Sci, 18.","DOI":"10.3390\/ijms18102208"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Girault, M.S., Dupuis, S., Ialy-Radio, C., Stouvenel, L., Viollet, C., Pierre, R., Favier, M., Ziyyat, A., and Barbaux, S. (2021). Deletion of the Spata3 Gene Induces Sperm Alterations and In Vitro Hypofertility in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041959"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e45991","DOI":"10.15252\/embr.201845991","article-title":"SPATC1L maintains the integrity of the sperm head-tail junction","volume":"19","author":"Kim","year":"2018","journal-title":"EMBO. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/biolre\/ioaa040","article-title":"Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male micedagger","volume":"103","author":"Nozawa","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6289","DOI":"10.1074\/jbc.RA119.012375","article-title":"The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis","volume":"295","author":"Gao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"jcs259036","DOI":"10.1242\/jcs.259036","article-title":"Transcription factor-like 5 is a potential DNA- and RNA-binding protein essential for maintaining male fertility in mice","volume":"135","author":"Xu","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Feng, M., Bai, Y., Chen, Y., and Wang, K. (2020). Knockout of the Transducin-Like Enhancer of Split 6 Gene Affects the Proliferation and Cell Cycle Process of Mouse Spermatogonia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165827"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/biolre\/ioaa060","article-title":"Tmprss12 is required for sperm motility and uterotubal junction migration in micedagger","volume":"103","author":"Larasati","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/andr.12889","article-title":"Tsga10 is essential for arrangement of mitochondrial sheath and male fertility in mice","volume":"9","author":"Luo","year":"2021","journal-title":"Andrology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/mrd.23539","article-title":"TSSK3, a novel target for male contraception, is required for spermiogenesis","volume":"88","author":"Nayyab","year":"2021","journal-title":"Mol. Reprod. Dev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ajhg.2019.02.020","article-title":"Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice","volume":"104","author":"Liu","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41419-020-2235-4","article-title":"YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m(6)A\/mRNA pathway","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e00228-19","DOI":"10.1128\/MCB.00228-19","article-title":"ZFP628 Is a TAF4b-Interacting Transcription Factor Required for Mouse Spermiogenesis","volume":"40","author":"Gustafson","year":"2020","journal-title":"Mol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Nakasuji, T., Ogonuki, N., Chiba, T., Kato, T., Shiozawa, K., Yamatoya, K., Tanaka, H., Kondo, T., Miyado, K., and Miyasaka, N. (2017). Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006578"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Yamauchi, Y., Matsumura, T., Bakse, J., Holmlund, H., Blanchet, G., Carrot, E., Ikawa, M., and Ward, M.A. (2022). Loss of mouse Y chromosome gene Zfy1 and Zfy2 leads to spermatogenesis impairment, sperm defects, and infertility. Biol. Reprod., ioac057.","DOI":"10.1093\/biolre\/ioac057"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2910","DOI":"10.1038\/cddis.2017.228","article-title":"Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint","volume":"8","author":"Hu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/mrd.23314","article-title":"The testis-specific gene 1700102P08Rik is essential for male fertility","volume":"87","author":"Wu","year":"2020","journal-title":"Mol. Reprod. Dev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/molehr\/gag005","article-title":"Identification and characterization of a novel human testis-specific Golgi protein, NYD-SP12","volume":"9","author":"Xu","year":"2003","journal-title":"Mol. Hum. Reprod."},{"key":"ref_90","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_91","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s10815-016-0715-3","article-title":"A new mutation identified in SPATA16 in two globozoospermic patients","volume":"33","author":"ElInati","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Behvarz, M., Rahmani, S.A., Siasi Torbati, E., Danaei Mehrabad, S., and Bikhof Torbati, M. (2022). Association of CATSPER1, SPATA16 and TEX11 genes polymorphism with idiopathic azoospermia and oligospermia risk in Iranian population. BMC Med. Genom., 15.","DOI":"10.1186\/s12920-022-01197-w"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/35618","article-title":"Evidence for evolutionary conservation of sex-determining genes","volume":"391","author":"Raymond","year":"1998","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/45130","article-title":"Conservation of a sex-determining gene","volume":"402","author":"Smith","year":"1999","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/dbio.1999.9461","article-title":"Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development","volume":"215","author":"Raymond","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0925-4773(99)00267-1","article-title":"Male specific expression suggests role of DMRT1 in human sex determination","volume":"91","author":"Moniot","year":"2000","journal-title":"Mech. Dev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.scr.2017.07.026","article-title":"DMRT proteins and coordination of mammalian spermatogenesis","volume":"24","author":"Zhang","year":"2017","journal-title":"Stem. Cell Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/mgme.2000.3060","article-title":"Deletions of 9p and the quest for a conserved mechanism of sex determination","volume":"71","author":"Ottolenghi","year":"2000","journal-title":"Mol. Genet. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/hmg\/8.6.989","article-title":"A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators","volume":"8","author":"Raymond","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_100","first-page":"3094","article-title":"Sex-determining gene(s) on distal 9p: Clinical and molecular studies in six cases","volume":"85","author":"Muroya","year":"2000","journal-title":"J. Clin. Endocrinol Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ydbio.2007.04.046","article-title":"Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation","volume":"307","author":"Kim","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1101\/gad.220194.113","article-title":"Regulation of pluripotency in male germline stem cells by Dmrt1","volume":"27","author":"Takashima","year":"2013","journal-title":"Genes Dev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1111\/jcmm.12838","article-title":"MicroRNA-224 regulates self-renewal of mouse spermatogonial stem cells via targeting DMRT1","volume":"20","author":"Cui","year":"2016","journal-title":"J. Cell Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zhang, T., Oatley, J., Bardwell, V.J., and Zarkower, D. (2016). DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006293"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1534\/genetics.114.163667","article-title":"Efficient and heritable gene targeting in tilapia by CRISPR\/Cas9","volume":"197","author":"Li","year":"2014","journal-title":"Genetics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1095\/biolreprod.112.103135","article-title":"A Wt1-Dmrt1 transgene restores DMRT1 to sertoli cells of Dmrt1(-\/-) testes: A novel model of DMRT1-deficient germ cells","volume":"88","author":"Agbor","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ajhg.2011.01.018","article-title":"DPY19L2 deletion as a major cause of globozoospermia","volume":"88","author":"Koscinski","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Yassine, S., Escoffier, J., Abi Nahed, R., Pierre, V., Karaouzene, T., Ray, P.F., and Arnoult, C. (2015). Dynamics of Sun5 localization during spermatogenesis in wild type and Dpy19l2 knock-out mice indicates that Sun5 is not involved in acrosome attachment to the nuclear envelope. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118698"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/brv.12498","article-title":"Nuclear envelope dynamics during mammalian spermatogenesis: New insights on male fertility","volume":"94","author":"Pereira","year":"2019","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ajhg.2011.02.007","article-title":"A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation","volume":"88","author":"Harbuz","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/molehr\/gat018","article-title":"DPY19L2 gene mutations are a major cause of globozoospermia: Identification of three novel point mutations","volume":"19","author":"Zhu","year":"2013","journal-title":"Mol. Hum. Reprod."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1093\/humrep\/des160","article-title":"MLPA and sequence analysis of DPY19L2 reveals point mutations causing globozoospermia","volume":"27","author":"Coutton","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13039-020-00495-1","article-title":"Identification of a novel deletion mutation in DPY19L2 from an infertile patient with globozoospermia: A case report","volume":"13","author":"Li","year":"2020","journal-title":"Mol. Cytogenet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e1900007","DOI":"10.1002\/prca.201900007","article-title":"Proteomic Analysis of Dpy19l2-Deficient Human Globozoospermia Reveals Multiple Molecular Defects","volume":"13","author":"Guo","year":"2019","journal-title":"Proteomics Clin. Appl."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"jcs259206","DOI":"10.1242\/jcs.259206","article-title":"FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice","volume":"134","author":"Castaneda","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4103\/aja.aja_79_18","article-title":"Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility","volume":"21","author":"Shang","year":"2019","journal-title":"Asian J. Androl."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1093\/humrep\/det005","article-title":"Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the DPY19L2 status","volume":"28","author":"Kuentz","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0378-1119(00)00519-9","article-title":"Identification and characterisation of a novel gene, TSGA10, expressed in testis","volume":"262","author":"Modarressi","year":"2001","journal-title":"Gene"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1095\/biolreprod.103.021170","article-title":"Tsga10 encodes a 65-kilodalton protein that is processed to the 27-kilodalton fibrous sheath protein","volume":"70","author":"Modarressi","year":"2004","journal-title":"Biol. Reprod."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/cge.13140","article-title":"TSGA10 is a novel candidate gene associated with acephalic spermatozoa","volume":"93","author":"Sha","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1007\/s10815-021-02295-x","article-title":"Pathogenesis of acephalic spermatozoa syndrome caused by splicing mutation and de novo deletion in TSGA10","volume":"38","author":"Xiang","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/cge.13747","article-title":"Novel mutations in PMFBP1, TSGA10 and SUN5: Expanding the spectrum of mutations that may cause acephalic spermatozoa","volume":"97","author":"Liu","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e1284","DOI":"10.1002\/mgg3.1284","article-title":"Loss-of-function mutation in TSGA10 causes acephalic spermatozoa phenotype in human","volume":"8","author":"Ye","year":"2020","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1007\/s43032-021-00648-6","article-title":"TSGA10 as a Potential Key Factor in the Process of Spermatid Differentiation\/Maturation: Deciphering Its Association with Autophagy Pathway","volume":"28","author":"Asgari","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.stem.2013.10.016","article-title":"Correction of a genetic disease in mouse via use of CRISPR-Cas9","volume":"13","author":"Wu","year":"2013","journal-title":"Cell Stem. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/cr.2014.160","article-title":"Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells","volume":"25","author":"Wu","year":"2015","journal-title":"Cell Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s13287-019-1386-7","article-title":"Restore natural fertility of Kit(w)\/Kit(wv) mouse with nonobstructive azoospermia through gene editing on SSCs mediated by CRISPR-Cas9","volume":"10","author":"Li","year":"2019","journal-title":"Stem. Cell Res. Ther."},{"key":"ref_128","first-page":"bio056804","article-title":"Establishment of Etv5 gene knockout mice as a recipient model for spermatogonial stem cell transplantation","volume":"10","author":"Zhang","year":"2021","journal-title":"Biol. Open"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/s41422-018-0074-y","article-title":"Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis","volume":"28","author":"Chen","year":"2018","journal-title":"Cell Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11427-019-1572-7","article-title":"Recent advances in mammalian reproductive biology","volume":"63","author":"Wen","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.02.012","article-title":"The regulation of spermatogenesis by androgens","volume":"30","author":"Smith","year":"2014","journal-title":"Semin. Cell Dev. Biol"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/biolre\/ioy077","article-title":"Spermatogonial stem cells","volume":"99","author":"Kubota","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3109\/19396368.2012.691943","article-title":"Spermatogenesis in mammals: Proteomic insights","volume":"58","author":"Chocu","year":"2012","journal-title":"Syst. Biol. Reprod. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/6\/1000\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:34Z","timestamp":1760138614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/6\/1000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":133,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["genes13061000"],"URL":"https:\/\/doi.org\/10.3390\/genes13061000","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]}}}