Academic Journal
Exosome Nanotherapy Rescues Male Fertility by Delivering Integrin β1 to Repair Environmental Stress-Damaged Testes.
| Τίτλος: | Exosome Nanotherapy Rescues Male Fertility by Delivering Integrin β1 to Repair Environmental Stress-Damaged Testes. |
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| Συγγραφείς: | Meng J; School of Public Health, North China University of Science and technology, Tangshan 063200, China.; Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China.; Hebei Key Laboratory of Coal Health and Safety, Tangshan 063200, China., Wang J; School of Public Health, North China University of Science and technology, Tangshan 063200, China.; Hebei Key Laboratory of Coal Health and Safety, Tangshan 063200, China., Li Z; School of Public Health, North China University of Science and technology, Tangshan 063200, China.; Hebei Key Laboratory of Coal Health and Safety, Tangshan 063200, China., Li F; School of Public Health, North China University of Science and technology, Tangshan 063200, China., Yun X; School of Public Health, North China University of Science and technology, Tangshan 063200, China., Jin Y; School of Public Health, North China University of Science and technology, Tangshan 063200, China.; Hebei Key Laboratory of Coal Health and Safety, Tangshan 063200, China., Zhang L; Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China.; Shandong Provincial Key Medical and Health Laboratory of Women's Occupational Exposure and Fertility Preservation, Jinan 250001, China. |
| Πηγή: | Molecular pharmaceutics [Mol Pharm] 2026 Jul 06; Vol. 23 (7), pp. 3951-3966. Date of Electronic Publication: 2026 Jun 08. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Chemical Society, c2004- |
| Ιατρικοί όροι (MeSH): | Integrin beta1*/metabolism , Integrin beta1*/administration & dosage , Testis*/metabolism , Testis*/drug effects , Testis*/pathology , Exosomes*/metabolism , Infertility, Male*/therapy , Infertility, Male*/metabolism , Fertility*/drug effects, Macrophages/metabolism ; Cytoskeleton/metabolism ; Spermatocytes/metabolism ; Spermatogenesis/drug effects ; Male ; Animals ; Mice ; Mice, Inbred C57BL |
| Περίληψη: | Environmental thermal-mechanical (T&M) stress threatens male fertility globally, yet no molecular therapies exist for stress-induced testicular damage. We demonstrate that macrophage-derived exosomes (Mφ-EVs) function as precision nanomedicines restoring fertility by delivering Integrin β1 (ITGB1) to repair damaged spermatogenic cytoskeletons. Using validated T&M stress models in C57BL/6 mice and GC-2 spermatocytes, we characterized severe reproductive dysfunction: 14.4% motility reduction (83.0 ± 2.0% to 71.3 ± 1.7%), 69.2% increased abnormalities (8.7 ± 2.3% to 14.7 ± 2.3%), and disrupted cytoskeletal homeostasis with Layilin (2.87-fold), Talin (3.90-fold), and Vinculin (4.24-fold) upregulation (P < 0.05). Mφ-EVs treatment achieved remarkable therapeutic efficacy: motility recovered to 80.8 ± 6.8%, abnormalities normalized to 11.6 ± 1.6% (all P < 0.05). Biodistribution tracking showed that exosomes accumulate in testicular tissue (peak 8 h). Molecular docking and cellular thermal shift assays revealed exosomal ITGB1 forms high-affinity ITGA1 complexes (score -222.76), stabilizing protein structure and normalizing cytoskeletal expression. This first proof-of-concept establishes exosome-based nanotherapy as a clinically translatable, noninvasive intervention for occupational and climate-related fertility disorders, with scalable manufacturing addressing millions of men worldwide. |
| Contributed Indexing: | Keywords: Cytoskeletal remodeling; Integrin β1; Macrophage-derived exosome; Male infertility; Thermal-mechanical stress |
| Substance Nomenclature: | 0 (Integrin beta1) 0 (Itgb1 protein, mouse) |
| Entry Date(s): | Date Created: 20260608 Date Completed: 20260706 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13344300 |
| DOI: | 10.1021/acs.molpharmaceut.6c00656 |
| PMID: | 42258346 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1543-8392 |
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| DOI: | 10.1021/acs.molpharmaceut.6c00656 |