Role of autophagy in cadmium-induced testicular injury

• Published in: Human & experimental toxicology 2017-10, Vol.36 (10), p.1039-1048
• Main Authors: Wang, Y-J, Yan, J, Yin, F, Li, L, Qin, Y-G, Meng, C-Y, Lu, R-F, Guo, L
• Format: Article
• Language: English
• Subjects: Animals; Atrophy; Autophagy; Autophagy - drug effects; Beclin-1 - metabolism; Body weight; Cadmium; Cadmium - toxicity; Cadmium chloride; Calcium; Exposure; Immunofluorescence; Injuries; Light levels; Male; Microtubule-associated protein 1; Microtubule-Associated Proteins - metabolism; Phagocytosis; Pipes; Proteins; Rats; Rats, Wistar; Receptors, Calcium-Sensing - metabolism; Rodents; Spectral analysis; Stem cell transplantation; Stem cells; Studies; Testes; Testis - drug effects; Testis - metabolism; Testis - pathology
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327116678300

The testis is sensitive to cadmium, but studies investigating cadmium-induced testicular injury have not yet clearly revealed the underlying mechanisms. This study aimed to investigate the injurious effects of cadmium on rat testes and the role that autophagy plays in this process. Wistar rats were randomly divided into four groups and intraperitoneally injected with 0.2 (low), 0.4 (middle), and 0.8 mg/kg·body weight (high) cadmium chloride for 5 weeks, while the control rats were injected with equal volume of saline. Rats exposed to cadmium appeared inactive and had reduced body weights and increased testicular organ coefficients at the end of treatment compared with control rats. Atomic absorption results showed that cadmium levels increased with increased cadmium exposure. Hematoxylin and eosin staining of testicular sections showed seminiferous tubular atrophy, decreased pipe diameter, spermatogonial stem cells falling off the inner lining, and reduced germ cell layers of disorderly arrangements in cadmium-treated rats. Immunohistochemical and western blot results both showed that levels of the autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3B) increased with increased cadmium exposure. We also found that LC3B-II and calcium-sensing receptor (CSR) levels in cadmium-exposed rats significantly increased. By immunofluorescence, we found that the percentage of cells that expressed the CSR was significantly higher in LC3B-positive than LC3B-negative cells. Together, our results showed that cadmium accumulates in the testes causing testicular injury, which may be related to increased autophagy levels. Furthermore, calcium disorders associated with the CSR may reveal a potential way to activate autophagy.