Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling
Abstract Type-2 diabetes mellitus (T2DM) is a complex metabolic disorder that adversely affects various physiological systems, particularly male reproductive health. Research indicates that T2DM increases the risk of retrograde ejaculation, impairing sexual function and fertility. Dysregulation of l...
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BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06590-4 |
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| author | Yi Yu Peng-Fei Liu Ming-Wei Zhan Yao-Qi Chen Yu-Qi Lai Lei Wang Jun-Jie Wu Fan Yao Xue-Qin Chen Xue-Jun Shang Ke-Rong Wu |
| author_facet | Yi Yu Peng-Fei Liu Ming-Wei Zhan Yao-Qi Chen Yu-Qi Lai Lei Wang Jun-Jie Wu Fan Yao Xue-Qin Chen Xue-Jun Shang Ke-Rong Wu |
| author_sort | Yi Yu |
| collection | DOAJ |
| description | Abstract Type-2 diabetes mellitus (T2DM) is a complex metabolic disorder that adversely affects various physiological systems, particularly male reproductive health. Research indicates that T2DM increases the risk of retrograde ejaculation, impairing sexual function and fertility. Dysregulation of lysyl oxidase (LOX) has been linked to diabetes-related complications in the male reproductive system. However, its role in seminal vesicle remains unclear. This study investigates LOX’s involvement in diabetes-related seminal vesicle pathology using human and mouse models. We assessed LOX expression in the seminal vesicles of men with T2DM and created a T2DM mouse model to observe changes. Our findings revealed elevated LOX expression in the seminal vesicles of T2DM men, accompanied by epithelial atrophy and fibrosis. Similarly, T2DM mice displayed significant atrophy and fibrosis of the seminal vesicles, correlated with increased LOX levels. Treatment with the LOX inhibitor, β-aminopropionitrile (BANP), significantly improved extracellular matrix remodeling and normalized the architecture of the seminal vesicles. Besides, LOX inhibition led to a significant reduction in T lymphocyte infiltration and apoptosis in the seminal vesicle epithelium of T2DM mice.These results highlight LOX’s critical role in seminal vesicle fibrosis associated with T2DM. Targeting LOX may provide a promising therapeutic strategy to alleviate reproductive complications and preserve reproductive health in men with T2DM. Graphical abstract |
| format | Article |
| id | doaj-art-9e9a9bf4e1f944cc86b8a575a8ab8552 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-9e9a9bf4e1f944cc86b8a575a8ab85522025-08-20T04:03:07ZengBMCJournal of Translational Medicine1479-58762025-07-0123111510.1186/s12967-025-06590-4Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signalingYi Yu0Peng-Fei Liu1Ming-Wei Zhan2Yao-Qi Chen3Yu-Qi Lai4Lei Wang5Jun-Jie Wu6Fan Yao7Xue-Qin Chen8Xue-Jun Shang9Ke-Rong Wu10Center for Reproductive Medicine, The First Affiliated Hospital of Ningbo UniversityDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, The First Affiliated Hospital of Ningbo UniversityDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandCenter for Reproductive Medicine, The First Affiliated Hospital of Ningbo UniversityDepartment of Urology, Jinling Hospital, Nanjing University School of Medicine, General Hospital of Eastern Theater CommandDepartment of Urology, The First Affiliated Hospital of Ningbo UniversityAbstract Type-2 diabetes mellitus (T2DM) is a complex metabolic disorder that adversely affects various physiological systems, particularly male reproductive health. Research indicates that T2DM increases the risk of retrograde ejaculation, impairing sexual function and fertility. Dysregulation of lysyl oxidase (LOX) has been linked to diabetes-related complications in the male reproductive system. However, its role in seminal vesicle remains unclear. This study investigates LOX’s involvement in diabetes-related seminal vesicle pathology using human and mouse models. We assessed LOX expression in the seminal vesicles of men with T2DM and created a T2DM mouse model to observe changes. Our findings revealed elevated LOX expression in the seminal vesicles of T2DM men, accompanied by epithelial atrophy and fibrosis. Similarly, T2DM mice displayed significant atrophy and fibrosis of the seminal vesicles, correlated with increased LOX levels. Treatment with the LOX inhibitor, β-aminopropionitrile (BANP), significantly improved extracellular matrix remodeling and normalized the architecture of the seminal vesicles. Besides, LOX inhibition led to a significant reduction in T lymphocyte infiltration and apoptosis in the seminal vesicle epithelium of T2DM mice.These results highlight LOX’s critical role in seminal vesicle fibrosis associated with T2DM. Targeting LOX may provide a promising therapeutic strategy to alleviate reproductive complications and preserve reproductive health in men with T2DM. Graphical abstracthttps://doi.org/10.1186/s12967-025-06590-4Lysyl oxidaseType-2 diabetes mellitusTGF-β1Seminal vesicleFibrosisApoptosis |
| spellingShingle | Yi Yu Peng-Fei Liu Ming-Wei Zhan Yao-Qi Chen Yu-Qi Lai Lei Wang Jun-Jie Wu Fan Yao Xue-Qin Chen Xue-Jun Shang Ke-Rong Wu Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling Journal of Translational Medicine Lysyl oxidase Type-2 diabetes mellitus TGF-β1 Seminal vesicle Fibrosis Apoptosis |
| title | Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling |
| title_full | Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling |
| title_fullStr | Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling |
| title_full_unstemmed | Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling |
| title_short | Lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type-2 diabetes mellitus through TGF-β1 signaling |
| title_sort | lysyl oxidase promotes seminal vesicle atrophy and fibrosis in type 2 diabetes mellitus through tgf β1 signaling |
| topic | Lysyl oxidase Type-2 diabetes mellitus TGF-β1 Seminal vesicle Fibrosis Apoptosis |
| url | https://doi.org/10.1186/s12967-025-06590-4 |
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