{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:28:07Z","timestamp":1791340087062,"version":"4.3.1"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>\n                    Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood\u2013testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.\n                  <\/jats:p>","DOI":"10.4103\/aja202286","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T05:50:54Z","timestamp":1670910654000},"page":"474-483","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway"],"prefix":"10.4103","volume":"25","author":[{"given":"Hao-Yu","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China"},{"name":"The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510515, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China"},{"name":"The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Yang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China"},{"name":"The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China"},{"name":"The Third School of Clinical Medicine, 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