Effect of spermidine on ameliorating spermatogenic disorders in diabetic mice via regulating glycolysis pathway.

Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6 J mice were divided into four main groups: the control group (n = 10), the diabetic group (n = 10), the 2.5 mg/kg SPM-treated diabetic group (n = 10) and the 5 mg/kg SPM-treated diabetic group (n = 10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What's more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation.

Wang JY ，Ma D ，Luo M ，Tan YP ，Ou Zhong ，Tian G ，Lv YT ，Li MX ，Chen X ，Tang ZH ，Hu LL ，Lei XC ... -  《Reproductive Biology and Endocrinology》

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

Liu F ，Liao B ，Ling YL ，Meng XZ ，Wang JL ，Hu LL ，Luo XQ ，Yang FL ... -  《-》

Dendrobium nobile-derived polysaccharides ameliorate spermatogenic disorders in mice with streptozotocin-induced diabetes through regulation of the glycolytic pathway.

Dysfunction of spermatogenesis is a major complication of diabetes mellitus (DM). This study characterized the protective effects of Dendrobium nobile-derived polysaccharides (DNP) against spermatogenetic dysfunction in mice with streptozotocin (STZ)-induced diabetes. The diabetic mice had lower body and testicular mass, and fewer spermatozoa with a higher incidence of malformation. The testicular histology showed disordered narrow seminiferous tubules covering a smaller area, and fewer spermatogenic cells. Moreover, the qRT-PCR analysis indicated that DM was associated with high expression of the pro-apoptotic factor Bax and low expression of the anti-apoptotic factor Bcl-2 in the testes. The qRT-PCR and immunohistochemical analysis clarified that DM was also associated with low testicular expression of the Sertoli cell (SC) markers GATA-4, WT1, and vimentin, and genes encoding the glycolytic rate-limiting enzymes LDHA, PKM2, and HK2. DNP treatment increased the body and testicular masses, sperm count, and number of spermatogenic cells of the mice, and reduced the proportion of abnormal sperm. DNP also reduced the expression of Bax, and increased that of Bcl-2, GATA-4, WT1, vimentin, LDHA, PKM2, and HK2, in the testes of the diabetic mice. Thus, DNP protects against spermatogenic dysfunction in diabetic mice by inhibiting apoptosis and activating the glycolytic pathway in their testes.

Luo M ，Liao B ，Ma D ，Wang J ，Wang J ，Liu J ，Lei X ，Cai Y ，Tang L ，Zhao L ，Long S ，Yang F ，Lei X ... -  《-》

Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway.

Ma D ，Hu L ，Wang J ，Luo M ，Liang A ，Lei X ，Liao B ，Li M ，Xie M ，Li H ，Gong Y ，Zi D ，Li X ，Chen X ，Liao X ... -  《-》

Lycium barbarum Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats.

The objective of this study was to investigate the protective effects of Lycium barbarum polysaccharides (LBP) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats. Compared to the control group, blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats. Further, the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats. Pathological changes were also observed in the spermatogenic tubules, along with a decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) expression, and increased cell apoptosis in the testes. Compared to the saline-treated diabetic rat group, metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function. After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes. The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1α) in diabetic testes were also upregulated by metformin or LBP treatment. In summary, LBP exerted protective effects by increasing cell proliferation, inhibiting cell apoptosis, and regulating SIRT1/HIF-1α expression in the testes of diabetic rats.

Lei X ，Huo P ，Wang Y ，Xie Y ，Shi Q ，Tu H ，Yao J ，Mo Z ，Zhang S ... -  《Frontiers in Endocrinology》