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Mitochondrial dysfunction affects male infertility, suggesting a relationship between the electron transfer chain and male infertility. COXFA4L3 (C15ORF48) is an emerging subunit protein of cytochrome oxidase specifically expressed in germ cells during spermatogenesis, and it may be involved in male infertility. Therefore, to investigate whether COXFA4L3 could be a marker of mitochondrial dysfunction in the sperm, this study examined the protein expression and localization profile of COXFA4L3 in the sperm of male patients with infertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010seven semen samples from a male infertility clinic at the Reproductive Center of Yokohama City University Medical Center were used to analyze sperm quality parameters and the expression and localization of energy production\u2010related proteins. These data were compared with the outcomes of infertility treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression levels of COXFA4L3 varied significantly between samples. Furthermore, COXFA4L3 was ectopically localized to the acrosome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ectopic expression of COXFA4L3 and PNA\u2010stained acrosomes may be useful parameters for fertility treatment selection. Assessing the acrosomal localization of COXFA4L3 will expedite pregnancy treatment planning.<\/jats:p><\/jats:sec>","DOI":"10.1002\/rmb2.12602","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T08:43:43Z","timestamp":1730277823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ectopic expression of the mitochondrial protein COXFA4L3 in human sperm acrosome and its potential application in the selection of male infertility treatments"],"prefix":"10.1002","volume":"23","author":[{"given":"Yusuke","family":"Fujisawa","sequence":"first","affiliation":[{"name":"Graduate School of Engineering Science Yokohama National University  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Life Science Laboratory, Technology and Development Division Kanto Chemical Co., Inc.  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