{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:25:31Z","timestamp":1768479931599,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of the Republic of China","award":["MOST 106-2320-B-030-003-MY3, MOST 105-2314-B -030-001-, MOST 104-2314-B-030-001-, and MOST 103-2314-B-030-002-"],"award-info":[{"award-number":["MOST 106-2320-B-030-003-MY3, MOST 105-2314-B -030-001-, MOST 104-2314-B-030-001-, and MOST 103-2314-B-030-002-"]}]},{"name":"Shin-Kong Wu Ho-Su Memorial Hospital","award":["104\u2010SKH\u2010FJU\u201005"],"award-info":[{"award-number":["104\u2010SKH\u2010FJU\u201005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Male infertility is observed in approximately 50% of all couples with infertility. Intracytoplasmic sperm injection (ICSI), a conventional artificial reproductive technique for treating male infertility, may fail because of a severe low sperm count, immotile sperm, immature sperm, and sperm with structural defects and DNA damage. Our previous studies have revealed that mutations in the septin (SEPT)-coding gene SEPT12 cause teratozoospermia and severe oligozoospermia. These spermatozoa exhibit morphological defects in the head and tail, premature chromosomal condensation, and nuclear damage. Sperm from Sept12 knockout mice also cause the developmental arrest of preimplantation embryos generated through in vitro fertilization and ICSI. Furthermore, we found that SEPT12 interacts with SPAG4, a spermatid nuclear membrane protein that is also named SUN4. Loss of the Spag4 allele in mice also disrupts the integration nuclear envelope and reveals sperm head defects. However, whether SEPT12 affects SPAG4 during mammalian spermiogenesis remains unclear. We thus conducted this study to explore this question. First, we found that SPAG4 and SEPT12 exhibited similar localizations in the postacrosomal region of elongating spermatids and at the neck of mature sperm through isolated murine male germ cells. Second, SEPT12 expression altered the nuclear membrane localization of SPAG4, as observed through confocal microscopy, in a human testicular cancer cell line. Third, SEPT12 expression also altered the localizations of nuclear membrane proteins: LAMINA\/C in the cells. This effect was specifically due to the expression of SEPT12 and not that of SEPT1, SEPT6, SEPT7, or SEPT11. Based on these results, we suggest that SEPT12 is among the moderators of SPAG4\/LAMIN complexes and is involved in the morphological formation of sperm during mammalian spermiogenesis.<\/jats:p>","DOI":"10.3390\/ijms20051163","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T04:58:35Z","timestamp":1552021115000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Testis-Specific SEPT12 Expression Affects SUN Protein Localization and is Involved in Mammalian Spermiogenesis"],"prefix":"10.3390","volume":"20","author":[{"given":"Chung-Hsin","family":"Yeh","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan"},{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Kae","family":"Wee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Sun","family":"Chiang","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"},{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao-Lin","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-1579","authenticated-orcid":false,"given":"Ying-Hung","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1091\/mbc.e03-04-0226","article-title":"Acroplaxome, an F-actin-keratin-containing plate, anchors the acrosome to the nucleus during shaping of the spermatid head","volume":"14","author":"Kierszenbaum","year":"2003","journal-title":"Mol. 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