NMN reverses diabetes-induced testicular dysfunction

Publishing in the Journal of Biochemistry and Biophysics, Liao and colleagues at South China University showed that treating diabetic male mice with Nicotinamide Mononucleotide (NMN) improved testicular structure and function and increased the abundance of viable sperm. In addition, the Chinese team showed that NMN restored the size of the tubes in the testis where sperm production occurs, and that key enzymes that use glucose as energy increased in quantity to improve testicular health. These findings suggest that NMN can reverse diabetes-induced male infertility.

NMN reverses diabetes-induced testicular dysfunction

Liao and colleagues fed mice a chemotherapeutic agent called streptozotocin, which is toxic to pancreatic cells and known to induce type 2 diabetes in mice. Their mouse model of diabetes showed a significant reduction in sperm count and a large increase in the proportion of abnormal sperm. Subsequent NMN treatment reversed the reduced sperm count and abnormal sperm abundance in diabetic mice.

(Ma et al., 2022 | Abs) NMN increases sperm count and reduces abnormal sperm. Diabetic mice (DM) showed significantly reduced sperm count (A) and increased abnormal sperm (B) compared with healthy mice (Ctrl), but NMN (DM+NMN) restored these defects.

(Ma et al., 2022 | Abs) NMN treatment restores the size of sperm-producing tubes. The area and diameter of the seminiferous tubules (the structures in the testes where sperm precursor cells are made) were reduced in diabetic mice (DM) compared to healthy mice (Ctrl), but restored by NMN treatment (DM+NMN).

To investigate NMN's ability to restore the structure of diabetic testes, Liao and colleagues examined the size of tubes in the testes called seminiferous tubules, where sperm precursor cells (sperm) are produced. Compared with mice without diabetes, mice with type 2 diabetes had significantly reduced seminiferous tubule area and diameter, but NMN cured these defects. As structural integrity confers functional capacity, these findings suggest that NMN can reverse diabetes-induced male infertility.

Because type II diabetes is associated with impaired breakdown of the sugar glucose for cellular energy in a process called glycolysis, Liao and colleagues examined the abundance of key glycolytic enzymes in the testes. While enzyme levels were drastically reduced in the testes of diabetic mice, NMNs restored their abundance. These results suggest that NMN restores glucose utilization in the testes of diabetic mice, which can provide the cellular energy needed for sperm production, potentially reversing infertility.

Antidiabetic drugs such as pioglitazone and metformin restore glycolysis in the testes, potentially restoring fertility in men with diabetes. The findings by Liao and colleagues suggest that NMN may provide another means to restore male fertility. Future studies should examine how pioglitazone, metformin, and NMN compare in restoring fertility in diabetic men.

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