Icariin protects testicular damage in streptozotocin-induced diabetic rats through regulation of glycolysis pathway.

OBJECTIVE: This study aims to investigate potential beneficial actions of icariin (ICA) on testicular spermatogenic function in male rats with streptozotocin (STZ)-induced diabetes and to explore the underlying mechanisms. Background: ICA was found to reduce blood glucose, regulate the endocrine function of the reproductive system, and improve testicular spermatogenic function. METHODS: Adult rats were intraperitoneally injected with STZ (65 mg/kg) to induce type 1 diabetes mellitus (T1DM). Diabetic rats were randomly classified intoT1DM (n = 6) and T1DM + ICA (n = 6) groups. Rats without STZ and ICA treatment were assigned as control group (n = 6). The morphology of testicular tissues was examined by histological staining. The mRNA and protein expression levels were determined by quantitative real-time PCR, Western blot and immunostaining, respectively. RESULTS: Rats from T1DM group showed a reduction in epididymis and testis weight, and a decrease in sperm count when compared to control group (p < 0.01), which was attenuated by ICA treatment (p < 0.05) Diabetic rats from T1DM group also exhibited reduced diameter and area of seminiferous tubules, along with decreased spermatogonia and primary spermatocytes number when compared to control group (p < 0.01), which was partially reversed by ICA treatment (p < 0.05) Rats from T1DM group exhibited down-regulation of PCNA mRNA and protein in the testis when compared to control group (p < 0.01); while ICA treatment up-regulated PCNA expression in the testis of diabetic rats compared to T1DM group (p < 0.05). Rats from T1DM group showed up-regulation of Bax and capase-3 and down-regulation of Bcl-2, PKM2, HK2 and lactate dehydrogenase A in the testes when compared to control group (p < 0.05), which was reversed by ICA treatment (p < 0.05). CONCLUSION: These findings suggest that ICA may exert its protective effects on testicular damage in diabetic rats through modulation of glycolysis pathway and suppression of apoptosis.

Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos.

Podophyllotoxin (PPT) is a kind of lignans extracted from the roots and stems of the genus Podophyllum from the tiller family, and it has been widely used in the treatment of condyloma acuminatum, multiple superficial epithelioma in the clinics. However, PPT has been reported to be toxic and can cause liver defects and other organ poisoning. In addition, emerging evidences also indicate that PPT has reproductive toxicity and causes female reproduction disorders. In this study, we used fertilized oocytes and tried to explore the effects of PPT on the early embryonic development with the mouse model. The results showed that exposure to PPT had negative effects on the cleavage of zygotes. Further analysis indicated that PPT could disrupt the organization of spindle and chromosome arrangement at the metaphase of first cleavage. We also found that PPT exposure to the zygotes induced excessive reactive oxygen species (ROS), suggesting the occurrence of oxidative stress. Moreover, in the PPT-exposed embryos, there was positive γH2A.X and Annexin-V signals, indicating that PPT induced embryonic DNA damage and early apoptosis. In conclusion, our results suggested that PPT could affect spindle formation and chromosome alignment during the first cleavage of mouse embryos, and its exposure induced DNA damage-mediated oxidative stress which eventually led to embryonic apoptosis, indicating the toxic effects of PPT on the early embryo development.