Cadmium-induced damage to primary cultures of rat Leydig cells.
The mechanism of testicular toxicity of cadmium is poorly understood. Previous studies focusing on cadmium-related changes in testicular histopathology have implicated testicular blood vessel damage as the main cause of cadmium toxicity. To further explore the toxic effects of cadmium on testis, we isolated and cultured rat Leydig cells, exposed to 10, 20, and 40 microM of cadmium chloride (base doses). After 24 h of exposure, cells and supernatants were harvested to examine cytotoxicity and genotoxicity of cadmium. The results show that both cell viability and concentration of testosterone excretion in primary Leydig cells are significantly lower in cadmium-exposed groups compared to the controls. Changes in testosterone excretion with human chorionic gonadotropin (hCG) stimulation is especially profound. The contents of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px) in exposed groups are significantly higher than those in the control group, but the activity of superoxide dismutase (SOD) is lower. The number of cells with DNA single strand breaks and the levels of cellular DNA damage in all three exposure groups are significantly higher than in controls. These results indicate that cadmium is directly toxic to primary Leydig cells, and that the decreased percentage of normal cells and the increased level of DNA damage in cadmium-exposed Leydig cells may be responsible for decreased testosterone secretion.
Yang
Jian-Ming
JM
Department of Toxicology, Shanghai Medical University, Shanghai 200032, PR China, jyang@scripps.edu
Arnush
Marc
M
Chen
Qiong-Yu
QY
Wu
Xiang-Dong
XD
Pang
Bing
B
Jiang
Xue-Zhi
XZ
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival; D002478:Cells, Cultured; D020552:Comet Assay; D003470:Culture Media; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000032:analysis; D013997:Time Factors
D003470:Culture Media; D009153:Mutagens; D002104:Cadmium; D013739:Testosterone; D008315:Malondialdehyde; D013482:Superoxide Dismutase