Geniposide attenuates spermatogenic dysfunction via inhibiting endoplasmic reticulum stress in male mice.

BACKGROUND: Spermatogenesis dysfunction is common in clinically infertile patients. Geniposide (GP) is one of the important active ingredients extracted from Eucommia ulmoides. However, the protective effect and mechanism of GP in the treatment of spermatogenic dysfunction is not known yet. METHODS: After cyclophosphamide-induced spermatogenic dysfunction was established in male mice, we gavaged GP for 4 weeks to evaluate spermatogenic function and anti-apoptotic effects by fertility, testicular weight, sperm quality, endoplasmic reticulum stress (ER stress), comet assay and serum testosterone level. RESULTS: GP can improve the damage of fertility and reproductive organs induced by cyclophosphamide and increase the number and activity of sperm. In comet assay, it was found that GP administration could alleviate sperm DNA damage induced by cyclophosphamide. In addition, GP treatment can significantly reduce ThT fluorescence intensity and improve endoplasmic reticulum stress induced by cyclophosphamide. Besides, TUNEL staining and WB showed that GP could inhibit the excessive apoptosis of cells and protect testis. (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: The protective effect of Geniposide on cyclophosphamide-induced spermatogenic dysfunction in mice is related to the inhibition of endoplasmic reticulum stress.

Protective Effects of Sesamin on Cytoxan-Induced Spermatogenesis Dysfunction by Regulating RNF8-ubH2A/ubH2B Pathways in Male Mice.

Most of the clinically infertile patients show spermatogenesis dysfunction. Cyclophosphamide, as an anticancer drug, can induce spermatogenesis dysfunction. Sesamin is the main bioactive component of natural lignans in sesame. It is abundant in sesame oil and has strong biological activities such as antioxidant, antibacterial, and hypoglycemic properties. By establishing the model of spermatogenic dysfunction induced by cyclophosphamide in male mice and then feeding sesamin (50, 100, and 200 mg/kg) for 2 weeks, we proved that sesamin can improve the reproductive organ damage induced by cyclophosphamide and increase the number and activity of sperms. Sesamin can resist cyclophosphamide-induced sperm nuclear maturity and DNA damage by increasing the expression levels of histones H2A and H2B in the testis. In addition, sesamin can improve the ubiquitination of histones regulated by RNF8 to protect the testis. In conclusion, these results suggest that sesamin can improve spermatogenic dysfunction induced by cyclophosphamide, which may be mediated by ubiquitination of histones.

Interplay between male reproductive system dysfunction and the therapeutic effect of flavonoids.

Male infertility has affected many families around the world. However, due to the mechanism underlying male reproductive system dysfunction are not completely elucidated, the use of drugs for male reproductive system dysfunction treatment only insignificant higher pregnancy outcomes, low-quality evidence suggests that clinical pregnancy rates may increase. Therefore, the focus in the future will be on developing more viable treatment options to prevent or treatment of male reproductive system dysfunction and achieve the purpose of improving fertility. Interestingly, natural products, as the potential inhibitors for the treatment of male reproductive system dysfunction, have shown a good therapeutic effect. Among many natural products, flavonoids have been extensively investigated for the treatment of male reproductive system dysfunction, such as testicular structural disruption, spermatogenesis disturbance and sperm quality decline. Flavonoids have been reported to have antioxidant, anti-inflammatory, immune stimulating, anti-apoptotic, anticarcinogenic, anti-allergic and antiviral activities, investigating for the treatment of male reproductive system dysfunction. In this review, we evaluate the therapeutic effects of flavonoids on male reproductive system dysfunction under different cellular scenarios and summarize the therapeutic strategies of flavonoids based on the aforementioned retrospective analysis. In the end, we describe some perspective research areas relevant to the application of flavonoids in the treatment of male reproductive system dysfunction.

Protective effects of Salidroside on spermatogenesis in streptozotocin induced type-1 diabetic male mice by inhibiting oxidative stress mediated blood-testis barrier damage.

Spermatogenic dysfunction is one of the major secondary complications of male diabetes. Salidroside (SAL) is the important active ingredients isolated from Herba Cistanche, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. The present study was designed to determine whether SAL contributes to the recovery from spermatogenic dysfunction in streptozotocin (STZ) induced type-1 diabetic mice. SAL (25, 50, or 100 mg/kg) and Clomiphene citrate (CC, 5 mg/kg) were orally administered to male type-1 diabetic mice for 10 weeks. Testis tissues were collected for histopathological and biochemical analysis. Moreover, reproductive organ weight, sperm parameters, and testicular cell DNA damage were estimated. The results revealed that SAL significantly improved the weight of the reproductive organs, sperm parameters and testicular morphology to different degrees in type-1 diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked downregulation the fluorescence expressions of p38 MAPK phosphorylation and upregulation the protein expressions of ZO-1, Occludin, Claudin-11 and N-cadherin after SAL administration (100 mg/kg) compared with the type-1 diabetic group. In conclusion, these results demonstrated that SAL exerts protective effects on type-1 diabetes-induced male spermatogenic dysfunction, which is likely mediated by inhibiting oxidative stress-mediated blood testis barrier damage.

Protective effects of betaine on diabetic induced disruption of the male mice blood-testis barrier by regulating oxidative stress-mediated p38 MAPK pathways.

BACKGROUND: Blood-testis barrier (BTB) impairments is one of the major secondary complications of diabetes. Betaine (BET) is the important active ingredients isolated from Lycium barbarum, which exhibits numerous pharmacological activities such as antioxidant, anti-diabetic, and anti-inflammatory effects. This study aimed to establish whether BET contributes to the recovery from BTB dysfunction in streptozotocin (STZ) induced diabetic mice. METHODS: BET (200, 400, 800 mg/kg) was orally administered to diabetic mice for 8 weeks. Testis tissues were collected for histopathological and biochemical analysis, the reproductive organ weight was estimated. Antioxidant enzyme activity and BTB associated protein expressions were determined with their corresponding assay kits and western blot analysis. The results revealed that BET significantly improved the weight of the reproductive organs and testicular morphology in diabetic mice. Furthermore, reactive oxygen species (ROS) and malondialdehyde (MDA) levels were significantly reduced, and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), markedly increased in the testicular tissue after SAL treatment. In addition, our data also showed a marked down-regulated the expressions of p38 MAPK phosphorylation and up-regulation the protein expressions of ZO-1, Occludin, Claudin-11, N-cadherin, and Connexin-43 after BET administration compared with the diabetic group. In conclusion, these results demonstrated that BET exerts protective effects on diabetes-induced BTB dysfunction, which may be through regulating oxidative stress-mediated p38 MAPK pathways.