{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:31:24Z","timestamp":1788233484449,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Funds Guiding Local Scientific and Technological Development","award":["250028"],"award-info":[{"award-number":["250028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Manganese (Mn) is a trace element essential for multiple physiological and biological processes. The testis plays a key role in male reproduction by producing sperm and synthesizing male hormones. This study investigates how Mn deficiency affects testicular development, spermatogenesis, and the blood\u2013testis barrier (BTB), and evaluates associated variations in oxidative stress to explore potential mechanisms. Methods: A Mn-deficient diet was used to induce Mn deficiency in mice, with MnCl2 administered via intraperitoneal injection. Mn levels in testicular tissue were measured by atomic absorption spectrometry. Testis and sperm morphology were assessed by H.E. and sperm staining. BTB markers were analyzed using immunofluorescence, Western blot, and qPCR. Oxidative stress was evaluated biochemically. Nrf2 pathway changes were detected by qPCR and Western blot. Results: The results indicated that Mn deficiency dramatically decreased the testicular index, caused abnormal testicular tissue structure, and significantly decreased Johnsen\u2019s score. At the same time, sperm density and motility were significantly reduced, and the sperm deformity rate was significantly increased. In addition, the BTB function was impaired, as indicated by the significantly down-regulated expression of tight junction proteins including Occludin, ZO-1, JAM-A, and Claudin-11. As the oxidative stress levels increased, the mRNA and protein expression levels of molecules (including Nrf2 and HO-1) related to the Nrf2 signaling pathway were significantly down-regulated, while its inhibitor Keap1 exhibited significantly up-regulated expression. Notably, after supplementing MnCl2, all the above abnormal indicators were significantly improved. Conclusions: Mn deficiency can lead to testicular tissue damage, decreased sperm quality, and BTB dysfunction, and the potential mechanism is probably closely associated with the increase in the oxidative stress level mediated by the Nrf2 pathway.<\/jats:p>","DOI":"10.3390\/nu17183007","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T10:05:17Z","timestamp":1758535517000},"page":"3007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Manganese Deficiency Causes Testicular Developmental Disorders, Blood\u2013Testis Barrier Damage, and Spermatogenesis Disruption via Nrf2-Mediated Oxidative Stress"],"prefix":"10.3390","volume":"17","author":[{"given":"Dianyi","family":"Peng","sequence":"first","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqing","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanchuan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6499-4499","authenticated-orcid":false,"given":"Jingbo","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/2277-8632.158577","article-title":"A review on role of essential trace elements in health and disease","volume":"4","author":"Prashanth","year":"2015","journal-title":"J. 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