Molybdenum and cadmium cause blood–testis barrier dysfunction through ROS-mediated NLRP3 inflammasome activation in sheep

In this study, 24 healthy male sheep were divided into four groups: the control group, Mo group (45 mg Mo·kg-1·BW), Cd group (1 mg Cd·kg-1·BW), and Mo + Cd group (45 mg Mo·kg-1·BW + 1 mg Cd·kg-1·BW). The experiment was last for 50 d. The results showed that Mo and Cd co-exposure induced histopathological changes and ultrastructural damage, decreased the mRNA and protein expression levels of BTB (blood-testis barrier)-related factors (CX-43, ZO-1, OCLN) ( P  < 0.05) and the T-SOD and CAT activity (P < 0.05), increased the MDA content (P < 0.05) and the proinflammatory factors levels (P < 0.05) in sheep testes. Moreover, the results showed that a sharp decline in BTB-related factors and antioxidase activity, and a significant increase in reactive oxygen species (ROS) levels ( P  < 0.05) and the expression levels of NLRP3 inflammasome-related factors (P < 0.05) in primary Sertoli cells (SCs) under Mo and Cd co-exposure. However, treatment with a ROS scavenger or NLRP3 inflammasome inhibitors could relieve BTB damage and oxidative injury, reduce the production of ROS ( P  < 0.05) and decrease the level of inflammatory factors (P < 0.05). Overall, these results indicated that Mo and Cd co-exposure reduced BTB-related protein levels and promoted ROS production and inflammatory reactions by activating the ROS/NLRP3 inflammasome pathway in sheep testes, which eventually induced reproductive toxicity.