Cadmium (Cd) and excess molybdenum (Mo) have multiple organ toxicity, and testis is one of their important target organs, but the reproductive toxicity of Mo and Cd combined treatment is still unclear. To explore the effects of Mo and Cd co-exposure on DNA damage and autophagy from the insight of ATM/AMPK/mTOR axis in duck testes, we randomly assigned 40 healthy 8-day-old ducks to control, Mo (100 mg/kg Mo), Cd (4 mg/kg Cd), and Mo + Cd groups for 16 weeks. Results found that Mo and/or Cd exposure caused trace elements imbalance, oxidative stress with a decrease in the activities of GSH-Px, CAT , T-SOD and GSH content, an increase in the concentrations of H 2 O 2 and MDA and pathological damage. Additionally, Mo and/or Cd markedly raised DNA damage-related factors expression levels and 8-OHdG content, caused G1/S arrest followed by decreasing CDK2 and Cyclin E protein levels and increasing CDK1 and Cyclin B protein levels, and activated ATM/AMPK/mTOR axis by enhancing p-ATM/ATM, p-AMPK/AMPK and reducing p-mTOR/mTOR protein levels, eventually triggered autophagy by elevating LC3A, LC3B, Atg5, Beclin-1 mRNA levels and LC3II/LC3I, Beclin-1 protein levels and reducing P62, Dynein, mTOR mRNA levels and P62 protein level. Moreover, these changes were most apparent in the combined group. Altogether, the results reveal that autophagy caused by Mo and/or Cd may be associated with activating the DNA damage-mediated ATM/AMPK/mTOR axis in duck testes, and Mo and Cd co-exposure exacerbates these changes.
Cadmium ( Cd ) and high molybdenum ( Mo ) are injurious to the body. Previous research has substantiated that Cd and Mo exposure caused testicular injury of ducks, but concrete mechanism is not fully clarified. To further survey the toxicity of co-exposure to Cd and Mo in testis, 40 healthy 8-day-old Shaoxing ducks ( Anas platyrhyncha ) were stochasticly distributed to four groups and raised with basic diet embracing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. At the 16th week, testis tissues were gathered. The characteristic ultrastructural changes related to apoptosis and ferroptosis were observed in Mo or Cd or both groups. Besides, Mo or Cd or both repressed nuclear factor erythroid 2-related factor 2( Nrf2 ) pathway via decreasing Nrf2, Heme oxygenase-1 ( HO-1 ), NAD(P)H quinone oxidoreductase 1 ( NQO1 ), Glutamate-cysteine ligase catalytic subunit ( GCLC ) and Glutamate-cysteine ligase modifier subunit ( GCLM ) mRNA expression of and Nrf2 protein expression, then stimulated apoptosis by elevating Bcl-2 antagonist/killer-1 ( Bak-1 ), Bcl-2-associated X-protein ( Bax ), Cytochrome complex ( Cyt-C ), caspase-3 mRNA expression, cleaved-caspase-3 protein expression and apoptosis rate, as well as reducing B-cell lymphoma-2 ( Bcl-2 ) mRNA expression and ratio of Bcl-2 to Bax, and triggered ferroptosis by upregulating Acyl-CoA Synthetase Long Chain Family Member 4 ( ACSL4 ), transferrin receptor ( TFR1 ) and Prostaglandin-Endoperoxide Synthase 2 ( PTGS2 ) expression levels, and downregulating ferritin heavy chain 1 ( FTH1 ), ferritin light chain 1 ( FTL1 ), ferroportin 1 ( FPN1 ), solute carrier family 7 member 11 ( SCL7A11 ) and glutathione peroxidase 4 ( GPX4 ) expression levels. The most obvious changes of these indexes were observed in co-treated group. Altogether, the results announced that Mo or Cd or both evoked apoptosis and ferroptosis by inhibiting Nrf2 pathway in the testis of ducks, and co-exposure to Mo and Cd exacerbated these variations.
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