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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,9]]},"abstract":"<jats:p>\n                    In mammals, sperm formation is completed in the seminiferous tubules within the testis, and sperm maturation occurs during the epididymal transit of the spermatozoa. Sperm morphology drastically changes when abnormal spermatozoa migrate from the testis to the epididymis. Detailed molecular mechanisms for sperm survival in the epididymis have not been determined yet. Globozoospermia is a cause of male infertility and is characterized by round-headed spermatozoa without acrosomes, an abnormal sperm nuclear membrane, and sperm midpiece defects.\n                    <jats:italic toggle=\"yes\">Testis expressed 50<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Tex50<\/jats:italic>\n                    ) is a testis-enriched gene that is expressed in mice and humans. Using CRISPR-Cas9, we generated\n                    <jats:italic toggle=\"yes\">Tex50<\/jats:italic>\n                    knockout (KO) mice and found that the KO males were sterile due to epididymal sperm malformations and impaired sperm motility. Surprisingly, electron microscopy, sperm morphology, and globozoospermia-related protein expression and localization in the KO testis were all normal. To understand this phenotype in more detail, we created TEX50-mCherry knockin mice to determine the localization of the TEX50 protein during spermatogenesis. The mCherry signals detected a ring-shaped structure surrounding the sperm acrosome and migrated to the posterior region of the sperm head. After the acrosome reaction, most of the spermatozoa retained mCherry signals. These results indicate that the\n                    <jats:italic toggle=\"yes\">Tex50<\/jats:italic>\n                    KO globozoospermia phenotype occurs after the migration of spermatozoa from the testis to the epididymis. We found that sperm membrane protein TEX50 is a putative key molecule to survive against globozoospermia-like malformations in the epididymis. It is essential for complete sperm formation and male fertility in mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2507930122","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T17:57:41Z","timestamp":1757008661000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Testis expressed 50 is essential for maintaining sperm acrosome integrity during epididymal transit"],"prefix":"10.1073","volume":"122","author":[{"given":"Saori","family":"Haga","sequence":"first","affiliation":[{"name":"Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferheen","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Department of Experimental Genome Research, The University of Osaka","place":["Suita, Osaka, Japan"]},{"name":"School of Medicine, University of California Davis","place":["Sacramento"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-3425","authenticated-orcid":false,"given":"Katarzyna","family":"Kent","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-362X","authenticated-orcid":false,"given":"Tsutomu","family":"Endo","sequence":"additional","affiliation":[{"name":"Graduate School of Agricultural and Life Sciences, Department of Animal Resource Sciences, The University of Tokyo","place":["Bunkyo-ku, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-5803","authenticated-orcid":false,"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Department of Experimental Genome Research, The University of Osaka","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":false,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, Department of Experimental Genome Research, The University of Osaka","place":["Suita, Osaka, Japan"]},{"name":"Center for Infectious Disease Education and Research, Division of Microbiology and Immunology, The University of Osaka","place":["Suita, Osaka, Japan"]},{"name":"The Institute of Medical Science, Laboratory of Reproductive Systems Biology, The University of Tokyo","place":["Minato-ku, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-8632","authenticated-orcid":false,"given":"Martin M.","family":"Matzuk","sequence":"additional","affiliation":[{"name":"Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-3507","authenticated-orcid":false,"given":"Yoshitaka","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical Technologies, National Cerebral and Cardiovascular Center","place":["Suita, Osaka, Japan"]},{"name":"Research Institute for Microbial Diseases, Department of Experimental Genome Research, The University of Osaka","place":["Suita, Osaka, Japan"]},{"name":"Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.17-0153"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41585"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.090613"},{"key":"e_1_3_4_4_2","unstructured":"R. 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