摘要
Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.
Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.
