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Here, we identify TECs as a central signaling hub that orchestrates intercellular communication within the human testis. Integrative single\u2010cell transcriptomic analysis of healthy and diabetic testes reveals that diabetes disrupts platelet\u2010derived growth factor (PDGF) signaling. TECs in diabetes undergo endothelial\u2010to\u2010mesenchymal transition and exhibit reduced\n                    <jats:italic>PDGFB<\/jats:italic>\n                    expression, while Leydig and testicular peritubular cells downregulate\n                    <jats:italic>PDGFRB<\/jats:italic>\n                    , collectively weakening intercellular connectivity. This disruption silences the JUND\u2010MCL1 survival program in Leydig cells, leading to apoptosis, extracellular matrix accumulation, and testosterone insufficiency, while impairing the contractility of testicular peritubular cells. Importantly, exogenous PDGF\u2010BB supplementation reactivates the JUND\u2010MCL1 axis, protects Leydig cells, alleviates fibrosis, and partially restores testosterone production and peritubular function. Together, these findings establish endothelial PDGF dysregulation as a key driver of diabetic testicular pathology and highlight PDGF\u2010BB supplementation as a mechanistically grounded therapeutic strategy to restore interstitial and endocrine function in the context of diabetes.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520114","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:34:06Z","timestamp":1770320046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial PDGF Signaling Dysregulation Impairs Testicular Interstitial Homeostasis in Diabetes"],"prefix":"10.1002","volume":"13","author":[{"given":"Wenxiu","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative 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