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In fact, many testis\u2010specific serine proteases, the largest family among the four protease families implicated in murine spermatogenesis, are indispensable for reproduction. In the present study, we demonstrate that the previously uncharacterized testis\u2010specific serine protease TRYX5 (1700074P13Rik) is required for male fertility in mice. <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> male mice are sterile, yet they have normal spermatogenesis and normal sperm parameters. In vivo fertilization experiments showed that the fertilization rate of <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> sperm was almost zero. Sperm counting and analysis of paraffin sections of oviducts revealed that <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/<\/jats:italic>\u2212<\/jats:sup> sperm were unable to migrate into the oviduct, which is likely the cause of the observed infertility of the <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/<\/jats:italic>\u2212<\/jats:sup> male mice. Importantly, we also found that there was almost no mature ADAM3 present in <jats:italic>Tryx5<\/jats:italic><jats:sup>\u2212<jats:italic>\/<\/jats:italic>\u2212<\/jats:sup> sperm and almost no ADAM3 precursor in <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/<\/jats:italic>\u2212<\/jats:sup> elongated spermatids of S13\u201016 stage, even though testes of <jats:italic>Tryx5<\/jats:italic><jats:sup><jats:italic>\u2212\/<\/jats:italic>\u2212<\/jats:sup> and wild type mice had the same amount of the total precursor ADAM3. Collectively, our results demonstrate that <jats:italic>Tryx5<\/jats:italic> is essential for male fertility in mice and suggest that TRYX5 functions in the stability or localization of ADAM3 precursor in elongated spermatids S13\u201016 stage, thereby regulating the ability of sperm to migrate from the uterus into the ampulla of the oviduct, the site of fertilization.<\/jats:p>","DOI":"10.1002\/jcp.29534","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T03:31:01Z","timestamp":1580873461000},"page":"6058-6072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Male fertility in <i>Mus musculus<\/i> requires the activity of TRYX5 in sperm migration into the oviduct"],"prefix":"10.1002","volume":"235","author":[{"given":"Haihang","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Conservation and Utilization of Subtropical Agro\u2010Bioresources 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