The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction / 亚洲男科学杂志(英文版)

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

Transcutaneous electrical acupoint stimulation for asthenozoospermia / 中华男科学杂志

Objective@#To study the effect of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of asthenozoospermia.@*METHODS@#We randomly divided 72 asthenozoospermia patients into a 2 Hz TEAS (n = 29), a 100 Hz TEAS (n = 20), and a blank control group (n = 23), those in the former two groups treated by 30 minutes of TEAS at 2 Hz and 100 Hz respectively, applied to the acupoints of bilateral Shenshu, left Zusanli, and Guanyuan, once a day for 60 days, while those in the blank control group left untreated. Using computer-assisted sperm analysis (CASA), we examined sperm concentration and motility as well as the percentages of grade a and grade a+b sperm in different groups of the patients.@*RESULTS@#Compared with the baseline, 2 Hz TEAS significantly increased sperm motility (［12.76 ± 1.39］ vs ［18.89 ± 2.46］%, P<0.05) and the percentage of grade a+b sperm ( ［10.68 ± 1.22］ vs ［16.32 ± 2.10］%, P<0.05) in the asthenozoospermic patients, while 100 Hz TEAS improved not only sperm motility (［12.32 ± 2.21］ vs ［23.81 ± 3.42］%, P<0.01) and the percentage of grade a+b sperm (［10.45 ± 1.98］ vs ［20.25 ± 2.82 ］%, P<0.01), but also the percentage of grade a sperm (［6.44 ± 1.16］ vs ［13.31 ± 2.30］%, P<0.05). Moreover, in comparison with the blank control group, 2 Hz TEAS also remarkably increased sperm motility (［9.57 ± 1.60］ vs ［18.89 ± 2.46］%, P<0.05) and the percentage of grade a+b sperm (［7.81 ± 1.31］ vs ［16.32 ± 2.10］%, P<0.05) in the asthenozoosperma patients, while 100 Hz TEAS improved not only sperm motility (［9.57 ± 1.60］ vs ［23.81 ± 3.42］%, P<0.01) and the percentage of grade a+b sperm (［7.81 ± 1.31］ vs ［20.25 ± 2.82］%, P<0.01) but also the percentage of grade a sperm (［4.87 ± 1.01］ vs ［13.31 ± 2.30］%, P<0.01). Meanwhile, the rate of clinical effectiveness was significantly higher in the 100 Hz TEASthan in the blank control group either in intention-to-treat (ITT) analysis (100% vs 18.18%) orper-protocol (PP) analysis (90% vs 0%), and so was it than in the 2 Hz TEAS group based on the data of ITT (100% vs 33.33%).@*CONCLUSIONS@#Both 2 Hz and 100 Hz TEAS are effective for the treatment of asthenozoospermia by improving sperm motility and vitality.