title: The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.
abstract: 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 GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), 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 NH 2 -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 GdCl 3 , 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.
authors.affiliation: Department of Emergency Surgery, The Daqing Oilfield General Hospital, Daqing, China.
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Kong
authors.affiliation: Department of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
authors.forename: Li-Quan
authors.initials: LQ
authors.lastname: Tong
authors.affiliation: Department of Emergency Surgery, The Fourth Hospital of Jilin University, Changchun, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Cao
authors.affiliation: Department of Urologic Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
authors.forename: Gong-Chen
authors.initials: GC
authors.lastname: Wang
authors.affiliation: Department of Urologic Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
authors.forename: Jin-Zhi
authors.initials: JZ
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Sun
authors.affiliation: Department of Urologic Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
authors.forename: Tie-Hui
authors.initials: TH
authors.lastname: Zhang
authors.affiliation: School of Nursing, Daqing Campus of Harbin Medical University, Daqing, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D007248:Infertility, Male / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008562:Membrane Glycoproteins; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000097:blood; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: D008562:Membrane Glycoproteins; D044169:Receptors, Calcium-Sensing; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D013739:Testosterone; D008315:Malondialdehyde; D013482:Superoxide Dismutase