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Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating
Duo Ma1,2, Linlin Hu3, Jinyuan Wang1,2
1Hunan Province Collaborative Innovation Base of Endocrinology & Metabolism Science and Education for Postgraduates, The First Affiliated Hospital of Shaoyang University and Hengyang Medical School, University of South China, Hengyang 422000, China.
Abstract:
Spermatogenic dysfunction is one of the major secondary complications of diabetes; however, the underlying mechanisms remain ill-defined, and there is no available drug or strategy for the radical treatment of diabetic spermatogenic dysfunction. Therefore, the objective of this study is to investigate the protective effects of nicotinamide mononucleotide (NMN) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic mice. The results show that oral administration of NMN significantly increases the body and testis weight and the number of sperms. Moreover, the abnormal sperm count and the rate of sperm malformation are significantly decreased compared with the saline-treated diabetic mice. Histological analysis reveals that NMN treatment significantly increases the area and diameter of seminiferous tubules, accompanied by an increased number of spermatogenic cells and sperms. Immunohistochemistry and qRT-PCR results show that NMN increases Bcl-2 expression and decreases Bax expression in the testis. NMN also increases the protein expression of Vimentin and the mRNA expressions of WT1 and GATA4. In addition, qRT-PCR, western blot analysis and immunohistochemistry results also show that NMN increases the expressions of glycolysis-related rate-limiting enzymes including HK2, PKM2, and LDHA. In summary, this study demonstrates the protective effects of NMN on the testis in an STZ-induced diabetic mice model. NMN exerts its protective effects via reducing spermatogenic cell apoptosis by regulating glycolysis of Sertoli cells in diabetic mice. This study provides an experimental basis for the future clinical application of NMN in diabetes-induced spermatogenic dysfunction.
Insights
Nicotinamide mononucleotide (NMN) protects against diabetes-induced testicular damage in mice. NMN treatment improves sperm count and quality by reducing apoptosis and regulating glycolysis in Sertoli cells.
Area of Science:
- Reproductive biology
- Endocrinology
- Metabolism
Background:
- Diabetes mellitus is a leading cause of secondary complications, including impaired spermatogenesis.
- The precise mechanisms underlying diabetic spermatogenic dysfunction are not fully understood.
- Current therapeutic strategies for diabetic reproductive complications are limited.
Purpose of the Study:
- To investigate the protective effects of nicotinamide mononucleotide (NMN) on testicular function in a mouse model of diabetes.
- To elucidate the molecular mechanisms by which NMN may ameliorate diabetic spermatogenic dysfunction.
Main Methods:
- Streptozotocin (STZ) was used to induce diabetes in mice.
- Mice were treated with NMN or saline.
- Evaluated body and testis weight, sperm count, and sperm morphology.
- Conducted histological analysis of testicular tissue.
- Utilized immunohistochemistry and qRT-PCR to assess gene and protein expression (Bcl-2, Bax, Vimentin, WT1, GATA4, HK2, PKM2, LDHA).
Main Results:
- NMN treatment significantly improved body and testis weight and increased sperm count in diabetic mice.
- NMN reduced abnormal sperm count and malformation rates.
- Histological examination showed increased seminiferous tubule size and spermatogenic cell numbers.
- NMN modulated apoptosis-related proteins (increased Bcl-2, decreased Bax) and key Sertoli cell markers (Vimentin, WT1, GATA4).
- NMN upregulated glycolysis-related enzymes (HK2, PKM2, LDHA) in the testis.
Conclusions:
- NMN demonstrates significant protective effects on testicular spermatogenic function in STZ-induced diabetic mice.
- NMN ameliorates diabetic testicular damage by reducing spermatogenic cell apoptosis and regulating Sertoli cell glycolysis.
- These findings support the potential clinical application of NMN for managing diabetes-induced spermatogenic dysfunction.
