Long-term copper exposure promotes apoptosis and autophagy by inducing oxidative stress in pig testis

Abstract

Copper (Cu) is a heavy metal which is being used widely in the industry and agriculture. However, the overuse of Cu makes it a common environmental pollutant. In order to investigate the testicular toxicity of Cu, the pigs were divided into three groups and were given Cu at 10 (control), 125, and 250 mg/kg body weight, respectively. The feeding period was 80 days. Serum hormone results showed that Cu exposure decreased the concentrations of follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increased the concentration of thyroxine (T4). Meanwhile, Cu exposure upregulated the expression of Cu transporter mRNA (Slc31a1, ATP7A, and ATP7B) in the testis, leading to increase in testicular Cu and led to spermatogenesis disorder. The Cu exposure led to an increased expression of antioxidant-related mRNA (Gpx4, TRX, HO-1, SOD1, SOD2, SOD3, CAT), along with increase in the MDA concentration in the testis. In LG group, the ROS in the testis was significantly increased. Furthermore, the apoptotic-related mRNA (Caspase3, Caspase8, Caspase9, Bax, Cytc, Bak1, APAF1, p53) and protein (Active Caspase3) and the autophagy-related mRNA (Beclin1, ATG5, LC3, and LC3B) expression increased after Cu exposure. The mitochondrial membrane potential in the testicular tissue decreased, while the number of apoptotic cells increased, as a result of oxidative stress. Overall, our study indicated that the Cu exposure promotes testicular apoptosis and autophagy by mediating oxidative stress, which is considered as the key mechanism causing testicular degeneration as well as dysfunction.

Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System

“…This finding indicated the occurrence of oxidative stress in the testicular tissue. The results of [ 26 ] showed that the results obtained after exposing pigs to 125 and 250 mg/kg of copper in the form of copper sulphate for 80 days were consistent with the results in the present study, i.e., the levels of MDA increased, and apoptosis and autophagy were promoted in the testes.…”

Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats

“…However, its extensive usage in many enterprises, such as, electronics, pesticides, building and transportation materials, water pipes and others incurred a notable eco-environmental contamination by polluting land and water resources [ 5 , 6 , 57 ]. Exposure to Cu compounds has been associated with adverse effects, including testicular oxidative stress, and apoptosis, along with declined sperm quality [ 19 , 24 ]. CUR has shown potent antioxidant properties and protected the testis against injury induced by various agents [ 26 , 27 , 41 , 42 , 43 ].…”

“…Although the effects of Cu on male fertility are not fully understood, excessive reactive oxygen species (ROS) and oxidative stress could play a significant role [19,24]. Given its rich content of highly unsaturated fatty acids, the testis is vulnerable to oxidative injury [25].…”

“…Reduced levels of circulating testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) have been demonstrated in immature male rats exposed to Cu for 26 days [ 23 ]. Although the effects of Cu on male fertility are not fully understood, excessive reactive oxygen species (ROS) and oxidative stress could play a significant role [ 19 , 24 ]. Given its rich content of highly unsaturated fatty acids, the testis is vulnerable to oxidative injury [ 25 ].…”

The Synergetic Effect of Egyptian Portulaca oleracea L. (Purslane) and Cichorium intybus L. (Chicory) Extracts against Glucocorticoid-Induced Testicular Toxicity in Rats through Attenuation of Oxidative Reactions and Autophagy

“…However, cumulative studies reveal that autophagy is a double-edged sword [ 25 ]. Autophagy disorder may also promote cytopathy, decreased serum testosterone, and cause sperm differentiation defects [ 26 ]. Thus, oxidative stress-induced autophagy is considered one of the proposed mechanisms for idiopathic male infertility [ 27 ].…”