{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:25:28Z","timestamp":1791962728573,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81971442"],"award-info":[{"award-number":["No. 81971442"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Backgrounds<\/jats:title><jats:p>Sterility induced by anti\u2010cancer treatments has caused significant concern, yet the mechanism and treatment exploration are little for male infertility after cancer therapy. Busulfan, the antineoplastic that was widely applied before bone marrow transplantation, was known to induce male reproductive disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the effect of busulfan on blood\u2013testis barrier function in adult rats and determine whether noncollagenous 1 domain peptide, the biologically active fragment proteolyzed from the collagen \u03b13 chain (IV) by matrix metalloproteinase 9, was involved during this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Adult male rats were treated with one\u2010dose or double\u2010dose of busulfan (10\u00a0mg\/kg) before euthanized at day 35. Blood\u2013testis barrier integrity assay, HE staining, immunofluorescence, and Western blot were used to validate the effect of busulfan on blood\u2013testis barrier permeability and spermatogenesis. JNJ0966 was applied to specifically inhibit the matrix metalloproteinase 9 activity. The polymerization activity of F\u2010actin\/G\u2010actin and microtubule\/tubulin in the testis were assessed by using commercial kits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A noteworthy blood\u2013testis barrier injury and significant up\u2010regulation of matrix metalloproteinase 9 activity and noncollagenous 1 level after a single\u2010dose busulfan (10\u00a0mg\/kg) treatment in adult rat testis were revealed. The application of JNJ0966 was found to decrease noncollagenous 1 level and rescue the busulfan\u2010induced blood\u2013testis barrier injury including the mis\u2010localization of junction proteins across the seminiferous epithelium, by recovering the organization and polymerization of both F\u2010actin and microtubule. The busulfan\u2010induced spermatogenesis impairment was also improved by JNJ0966.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings thus demonstrate that the elevation in matrix metalloproteinase 9 and noncollagenous 1 might participate in busulfan\u2010induced blood\u2013testis barrier disruption in adult male rats. As such, busulfan\u2010induced male infertility could possibly be managed through interventions on noncollagenous 1 production.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13112","type":"journal-article","created":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T07:10:21Z","timestamp":1631949021000},"page":"377-391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Busulfan impairs blood\u2013testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9"],"prefix":"10.1111","volume":"10","author":[{"given":"Shuyi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology College of Life Science China Medical University  Shenyang China"},{"name":"Center of Reproductive Medicine Shengjing Hospital of China Medical University  Shenyang 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