{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:49:42Z","timestamp":1761713382097,"version":"build-2065373602"},"reference-count":31,"publisher":"CSIRO Publishing","issue":"11","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":2994,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,3]]},"abstract":"<jats:p>Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1 \u00b5g mL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6\/TR) were co-microinjected into mouse testes to produce TetR&amp;shuPA mice model. Though oral gavage by 0.75 mg mL-1 Dox each day for 1 week, the Plau mRNA expression, uPA protein level and uPA enzyme activity in mice testis decreased significantly in TetR&amp;shuPA mice model. After Dox induction of 1 week, the TetR&amp;shuPA mice mated with female mice. Our results show that the pregnancy rate was reduced by approximately 40% and the sperm motility also decreased significantly. These data indicated that downregulation of uPA could decrease the fertility of male mice, which may be caused by a reduction in sperm motility. To investigate the reversible effect and safety of the inducible uPA shRNA system, we withdraw Dox and found the mating rate and sperm motility gradually recovered after 2 weeks. The histopathology structure of the testis, epididymis, and main organs was not altered significantly. The results of the present study indicating that uPA may be regarded as a novel target for the regulation of male fertility.<\/jats:p>","DOI":"10.1071\/rd16477","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T22:58:16Z","timestamp":1489618696000},"page":"2149-2156","source":"Crossref","is-referenced-by-count":8,"title":["Tissue-specific inhibition of urokinase-type plasminogen activator expression in the testes of mice by inducible lentiviral RNA interference causes male infertility"],"prefix":"10.1071","volume":"29","author":[{"given":"Kai","family":"Zhao","sequence":"first","affiliation":[{"name":"AFamily Planning Research Institute and Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"BWuhan Tongji Reproductive Medicine Hospital, Wuhan, 430014, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Xiong","sequence":"additional","affiliation":[{"name":"CDepartment of Physiology, Medical School of Jianghan University, Wuhan, 430056, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Hu","sequence":"additional","affiliation":[{"name":"AFamily Planning Research Institute and Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."},{"name":"BWuhan Tongji Reproductive Medicine Hospital, Wuhan, 430014, China."},{"name":"DCorresponding author. Email: hulian02@163.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-liang","family":"Xiong","sequence":"additional","affiliation":[{"name":"AFamily Planning Research Institute and Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."},{"name":"BWuhan Tongji Reproductive Medicine Hospital, Wuhan, 430014, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"67","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"2025102819313422000_R1","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1111\/J.1471-4159.2006.04013.X","article-title":"Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion.","volume":"98","author":"Bahi","year":"2006","journal-title":"J. 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