Plant-derived exosome-like nanovesicles improve testicular injury by alleviating cell cycle arrest in Sertoli cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Plant-derived exosome-like nanovesicles improve testicular injury by alleviating cell cycle arrest in Sertoli cells Yong Jiang, Xiao Zhang, Yuling xiao, Xingzi Hou, Chenlong Wei, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8050231/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The testis plays a vital role in male reproduction, and its function directly impacts spermatogenesis and male fertility. Cyclophosphamide, a commonly used chemotherapeutic agent, induces severe testicular toxicity; however, effective strategies for prevention or treatment are currently lacking. In this study, we isolated and identified exosome-like nanovesicles derived from Cistanche deserticola (CDELNs), characterized their composition, and investigated their therapeutic effects and molecular mechanisms on cyclophosphamide-induced testicular injury. Specifically, we found that CDELNs are preferentially taken up by testicular Sertoli cells, and this uptake process is mediated by heparan sulfate proteoglycans (HSPG). Mechanistically, miR159b-3p derived from CDELNs alleviates cell cycle arrest and restores testicular function by inhibiting the expression of the cell cycle inhibitor P21, thereby promoting the phosphorylation-dependent activation of cyclin-dependent kinase 1 (CDK1). Furthermore, single-cell transcriptomic analysis of testicular tissues from patients with non-obstructive azoospermia (NOA) in published database revealed that Sertoli cells and P21 are critically involved in male reproductive disorders, suggesting that CDELNs-based intervention strategy targeting P21 holds broad prospects for clinical translation. Collectively, our study reveals firstly that CDELNs, a novel bioactive substrate of Cistanche deserticola, exert therapeutic effects on male testicular injury by regulating the cell cycle pathway through their miRNA. Health sciences/Medical research Health sciences/Medical research/Drug development Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterials.pdf Plant-derived exosome-like nanovesicles improve testicular injury by alleviating cell cycle arrest in Sertoli cells Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8050231","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":545131994,"identity":"b285c042-4e3b-47d1-b3ba-c1f7a1602d28","order_by":0,"name":"Yong 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